Journal articles: 'RNA localization and translation'

1

Gáspár, Imre, and Anne Ephrussi. "RNA localization feeds translation." Science 357, no. 6357 (September 21, 2017): 1235–36. http://dx.doi.org/10.1126/science.aao5796.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Gavis, E. R., L. Lunsford, S. E. Bergsten, and R. Lehmann. "A conserved 90 nucleotide element mediates translational repression of nanos RNA." Development 122, no. 9 (September 1, 1996): 2791–800. http://dx.doi.org/10.1242/dev.122.9.2791.

Full text

Abstract:

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3′ untranslated region. We have identified a discrete translational control element within the nanos 3′ untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3′UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.

APA, Harvard, Vancouver, ISO, and other styles

3

Lasko, Paul. "Cup-ling oskar RNA localization and translational control." Journal of Cell Biology 163, no. 6 (December 22, 2003): 1189–91. http://dx.doi.org/10.1083/jcb.200311123.

Full text

Abstract:

RNA localization and spatially restricted translational control can serve to deploy specific proteins to particular places within a cell. oskar (osk) RNA is a key initiatior of posterior patterning and germ cell specification in Drosophila, and its localization and translation are under elaborate control. In this issue, Wilhelm et al. (2003) show that the protein Cup both promotes osk localization and participates in repressing translation of unlocalized osk.

APA, Harvard, Vancouver, ISO, and other styles

4

Rongo, C., E. R. Gavis, and R. Lehmann. "Localization of oskar RNA regulates oskar translation and requires Oskar protein." Development 121, no. 9 (September 1, 1995): 2737–46. http://dx.doi.org/10.1242/dev.121.9.2737.

Full text

Abstract:

The site of oskar RNA and protein localization within the oocyte determines where in the embryo primordial germ cells form and where the abdomen develops. Initiation of oskar RNA localization requires the activity of several genes. We show that ovaries mutant for any of these genes lack Oskar protein. Using various transgenic constructs we have determined that sequences required for oskar RNA localization and translational repression map to the oskar 3′UTR, while sequences involved in the correct temporal activation of translation reside outside the oskar 3′UTR. Upon localization of oskar RNA and protein at the posterior pole, Oskar protein is required to maintain localization of oskar RNA throughout oogenesis. Stable anchoring of a transgenic reporter RNA at the posterior pole is disrupted by oskar nonsense mutations. We propose that initially localization of oskar RNA permits translation into Oskar protein and that subsequently Oskar protein regulates its own RNA localization through a positive feedback mechanism.

APA, Harvard, Vancouver, ISO, and other styles

5

Rosana, Albert Remus R., Denise S. Whitford, Richard P. Fahlman, and George W. Owttrim. "Cyanobacterial RNA Helicase CrhR Localizes to the Thylakoid Membrane Region and Cosediments with Degradosome and Polysome Complexes in Synechocystis sp. Strain PCC 6803." Journal of Bacteriology 198, no. 15 (May 23, 2016): 2089–99. http://dx.doi.org/10.1128/jb.00267-16.

Full text

Abstract:

ABSTRACTThe cyanobacteriumSynechocystissp. strain PCC 6803 encodes a single DEAD box RNA helicase, CrhR, whose expression is tightly autoregulated in response to cold stress. Subcellular localization and proteomic analysis results indicate that CrhR localizes to both the cytoplasmic and thylakoid membrane regions and cosediments with polysome and RNA degradosome components. Evidence is presented that either functional RNA helicase activity or a C-terminal localization signal was required for polysome but not thylakoid membrane localization. Polysome fractionation and runoff translation analysis results indicate that CrhR associates with actively translating polysomes. The data implicate a role for CrhR in translation or RNA degradation in the thylakoid region related to thylakoid biogenesis or stability, a role that is enhanced at low temperature. Furthermore, CrhR cosedimentation with polysome and RNA degradosome complexes links alteration of RNA secondary structure with a potential translation-RNA degradation complex inSynechocystis.IMPORTANCEThe interaction between mRNA translation and degradation is a major determinant controlling gene expression. Regulation of RNA function by alteration of secondary structure by RNA helicases performs crucial roles, not only in both of these processes but also in all aspects of RNA metabolism. Here, we provide evidence that the cyanobacterial RNA helicase CrhR localizes to both the cytoplasmic and thylakoid membrane regions and cosediments with actively translating polysomes and RNA degradosome components. These findings link RNA helicase alteration of RNA secondary structure with translation and RNA degradation in prokaryotic systems and contribute to the data supporting the idea of the existence of a macromolecular machine catalyzing these reactions in prokaryotic systems, an association hitherto recognized only in archaea and eukarya.

APA, Harvard, Vancouver, ISO, and other styles

6

MARZI, S. "Ribosomal localization of translation initiation factor IF2." RNA 9, no. 8 (August 1, 2003): 958–69. http://dx.doi.org/10.1261/rna.2116303.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Bergsten, S. E., and E. R. Gavis. "Role for mRNA localization in translational activation but not spatial restriction of nanos RNA." Development 126, no. 4 (February 15, 1999): 659–69. http://dx.doi.org/10.1242/dev.126.4.659.

Full text

Abstract:

Patterning of the anterior-posterior body axis during Drosophila development depends on the restriction of Nanos protein to the posterior of the early embryo. Synthesis of Nanos occurs only when maternally provided nanos RNA is localized to the posterior pole by a large, cis-acting signal in the nanos 3′ untranslated region (3′UTR); translation of unlocalized nanos RNA is repressed by a 90 nucleotide Translational Control Element (TCE), also in the 3′UTR. We now show quantitatively that the majority of nanos RNA in the embryo is not localized to the posterior pole but is distributed throughout the cytoplasm, indicating that translational repression is the primary mechanism for restricting production of Nanos protein to the posterior. Through an analysis of transgenes bearing multiple copies of nanos 3′UTR regulatory sequences, we provide evidence that localization of nanos RNA by components of the posteriorly localized germ plasm activates its translation by preventing interaction of nanos RNA with translational repressors. This mutually exclusive relationship between translational repression and RNA localization is mediated by a 180 nucleotide region of the nanos localization signal, containing the TCE. These studies suggest that the ability of RNA localization to direct wild-type body patterning also requires recognition of multiple, unique elements within the nanos localization signal by novel factors. Finally, we propose that differences in the efficiencies with which different RNAs are localized result from the use of temporally distinct localization pathways during oogenesis.

APA, Harvard, Vancouver, ISO, and other styles

8

Rajgor, Dipen, and Catherine M. Shanahan. "RNA granules and cytoskeletal links." Biochemical Society Transactions 42, no. 4 (August 1, 2014): 1206–10. http://dx.doi.org/10.1042/bst20140067.

Full text

Abstract:

In eukaryotic cells, non-translating mRNAs can accumulate into cytoplasmic mRNP (messenger ribonucleoprotein) granules such as P-bodies (processing bodies) and SGs (stress granules). P-bodies contain the mRNA decay and translational repression machineries and are ubiquitously expressed in mammalian cells and lower eukaryote species including Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. In contrast, SGs are only detected during cellular stress when translation is inhibited and form from aggregates of stalled pre-initiation complexes. SGs and P-bodies are related to NGs (neuronal granules), which are essential in the localization and control of mRNAs in neurons. Importantly, RNA granules are linked to the cytoskeleton, which plays an important role in mediating many of their dynamic properties. In the present review, we discuss how P-bodies, SGs and NGs are linked to cytoskeletal networks and the importance of these linkages in maintaining localization of their RNA cargoes.

APA, Harvard, Vancouver, ISO, and other styles

9

Mansfield, Jennifer H., James E. Wilhelm, and Tulle Hazelrigg. "Ypsilon Schachtel, aDrosophilaY-box protein, acts antagonistically to Orb in theoskarmRNA localization and translation pathway." Development 129, no. 1 (January 1, 2002): 197–209. http://dx.doi.org/10.1242/dev.129.1.197.

Full text

Abstract:

Subcellular localization of mRNAs within the Drosophila oocyte is an essential step in body patterning. Yps, a Drosophila Y-box protein, is a component of an ovarian ribonucleoprotein complex that also contains Exu, a protein that plays an essential role in mRNA localization. Y-box proteins are known translational regulators, suggesting that this complex might regulate translation as well as mRNA localization. Here we examine the role of the yps gene in these events. We show that yps interacts genetically with orb, a positive regulator of oskar mRNA localization and translation. The nature of the genetic interaction indicates that yps acts antagonistically to orb. We demonstrate that Orb protein is physically associated with both the Yps and Exu proteins, and that this interaction is mediated by RNA. We propose a model wherein Yps and Orb bind competitively to oskar mRNA with opposite effects on translation and RNA localization.

APA, Harvard, Vancouver, ISO, and other styles

10

Anderson, Paul, and Nancy Kedersha. "RNA granules." Journal of Cell Biology 172, no. 6 (March 6, 2006): 803–8. http://dx.doi.org/10.1083/jcb.200512082.

Full text

Abstract:

Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay.

APA, Harvard, Vancouver, ISO, and other styles

11

Vazquez-Pianzola, Paula, and Beat Suter. "Conservation of the RNA Transport Machineries and Their Coupling to Translation Control across Eukaryotes." Comparative and Functional Genomics 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/287852.

Full text

Abstract:

Restriction of proteins to discrete subcellular regions is a common mechanism to establish cellular asymmetries and depends on a coordinated program of mRNA localization and translation control. Many processes from the budding of a yeast to the establishment of metazoan embryonic axes and the migration of human neurons, depend on this type of cell polarization. How factors controlling transport and translation assemble to regulate at the same time the movement and translation of transported mRNAs, and whether these mechanisms are conserved across kingdoms is not yet entirely understood. In this review we will focus on some of the best characterized examples of mRNA transport machineries, the “yeast locasome” as an example of RNA transport and translation control in unicellular eukaryotes, and on theDrosophilaBic-D/Egl/Dyn RNA localization machinery as an example of RNA transport in higher eukaryotes. This focus is motivated by the relatively advanced knowledge about the proteins that connect the localizing mRNAs to the transport motors and the many well studied proteins involved in translational control of specific transcripts that are moved by these machineries. We will also discuss whether the core of these RNA transport machineries and factors regulating mRNA localization and translation are conserved across eukaryotes.

APA, Harvard, Vancouver, ISO, and other styles

12

Yoon, Young J., Bin Wu, Adina R. Buxbaum, Sulagna Das, Albert Tsai, Brian P. English, Jonathan B. Grimm, Luke D. Lavis, and Robert H. Singer. "Glutamate-induced RNA localization and translation in neurons." Proceedings of the National Academy of Sciences 113, no. 44 (October 17, 2016): E6877—E6886. http://dx.doi.org/10.1073/pnas.1614267113.

Full text

Abstract:

Localization of mRNA is required for protein synthesis to occur within discrete intracellular compartments. Neurons represent an ideal system for studying the precision of mRNA trafficking because of their polarized structure and the need for synapse-specific targeting. To investigate this targeting, we derived a quantitative and analytical approach. Dendritic spines were stimulated by glutamate uncaging at a diffraction-limited spot, and the localization of single β-actin mRNAs was measured in space and time. Localization required NMDA receptor activity, a dynamic actin cytoskeleton, and the transacting RNA-binding protein, Zipcode-binding protein 1 (ZBP1). The ability of the mRNA to direct newly synthesized proteins to the site of localization was evaluated using a Halo-actin reporter so that RNA and protein were detected simultaneously. Newly synthesized Halo-actin was enriched at the site of stimulation, required NMDA receptor activity, and localized preferentially at the periphery of spines. This work demonstrates that synaptic activity can induce mRNA localization and local translation of β-actin where the new actin participates in stabilizing the expanding synapse in dendritic spines.

APA, Harvard, Vancouver, ISO, and other styles

13

Zhang, Linzhu, Yaguang Zhang, Su Zhang, Lei Qiu, Yang Zhang, Ying Zhou, Junhong Han, and Jiang Xie. "Translational Regulation by eIFs and RNA Modifications in Cancer." Genes 13, no. 11 (November 6, 2022): 2050. http://dx.doi.org/10.3390/genes13112050.

Full text

Abstract:

Translation is a fundamental process in all living organisms that involves the decoding of genetic information in mRNA by ribosomes and translation factors. The dysregulation of mRNA translation is a common feature of tumorigenesis. Protein expression reflects the total outcome of multiple regulatory mechanisms that change the metabolism of mRNA pathways from synthesis to degradation. Accumulated evidence has clarified the role of an increasing amount of mRNA modifications at each phase of the pathway, resulting in translational output. Translation machinery is directly affected by mRNA modifications, influencing translation initiation, elongation, and termination or altering mRNA abundance and subcellular localization. In this review, we focus on the translation initiation factors associated with cancer as well as several important RNA modifications, for which we describe their association with cancer.

APA, Harvard, Vancouver, ISO, and other styles

14

Pyhtila, B., T. Zheng, P. J. Lager, J. D. Keene, M. C. Reedy, and C. V. Nicchitta. "Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum." RNA 14, no. 3 (January 18, 2008): 445–53. http://dx.doi.org/10.1261/rna.721108.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Castagnetti, S., M. W. Hentze, A. Ephrussi, and F. Gebauer. "Control of oskar mRNA translation by Bruno in a novel cell-free system from Drosophila ovaries." Development 127, no. 5 (March 1, 2000): 1063–68. http://dx.doi.org/10.1242/dev.127.5.1063.

Full text

Abstract:

The coupled regulation of oskar mRNA localization and translation in time and space is critical for correct anteroposterior patterning of the Drosophila embryo. Localization-dependent translation of oskar mRNA, a mechanism whereby oskar RNA localized at the posterior of the oocyte is selectively translated and the unlocalized RNA remains in a translationally repressed state, ensures that Oskar activity is present exclusively at the posterior pole. Genetic experiments indicate that translational repression involves the binding of Bruno protein to multiple sites, the Bruno Response Elements (BRE), in the 3′ untranslated region (UTR) of oskar mRNA. We have established a cell-free translation system derived from Drosophila ovaries, which faithfully reproduces critical features of mRNA translation in vivo, namely cap structure and poly(A) tail dependence. We show that this ovary extract, containing endogenous Bruno, is able to recapitulate oskar mRNA regulation in a BRE-dependent way. Thus, the assembly of a ribonucleoprotein (RNP) complex leading to the translationally repressed state occurs in vitro. Moreover, we show that a Drosophila embryo extract lacking Bruno efficiently translates oskar mRNA. Addition of recombinant Bruno to this extract establishes the repressed state in a BRE-dependent manner, providing a direct biochemical demonstration of the critical role of Bruno in oskar mRNA translation. The approach that we describe opens new avenues to investigate translational regulation in Drosophila oogenesis at a biochemical level.

APA, Harvard, Vancouver, ISO, and other styles

16

Minshall, Nicola, Michel Kress, Dominique Weil, and Nancy Standart. "Role of p54 RNA Helicase Activity and Its C-terminal Domain in Translational Repression, P-body Localization and Assembly." Molecular Biology of the Cell 20, no. 9 (May 2009): 2464–72. http://dx.doi.org/10.1091/mbc.e09-01-0035.

Full text

Abstract:

The RNA helicase p54 (DDX6, Dhh1, Me31B, Cgh-1, RCK) is a prototypic component of P-(rocessing) bodies in cells ranging from yeast to human. Previously, we have shown that it is also a component of the large cytoplasmic polyadenylation element-binding protein translation repressor complex in Xenopus oocytes and that when tethered to the 3′ untranslated region, Xp54 represses reporter mRNA translation. Here, we examine the role of the p54 helicase activity in translational repression and in P-body formation. Mutagenesis of conserved p54 helicase motifs activates translation in the tethered function assay, reduces accumulation of p54 in P-bodies in HeLa cells, and inhibits its capacity to assemble P-bodies in p54-depleted cells. Similar results were obtained in four helicase motifs implicated in ATP binding and in coupling ATPase and RNA binding activities. This is accompanied by changes in the interaction of the mutant p54 with the oocyte repressor complex components. Surprisingly, the C-terminal D2 domain alone is sufficient for translational repression and complete accumulation in P-bodies, although it is deficient for P-body assembly. We propose a novel RNA helicase model, in which the D2 domain acts as a protein binding platform and the ATPase/helicase activity allows protein complex remodeling that dictates the balance between repressors and an activator of translation.

APA, Harvard, Vancouver, ISO, and other styles

17

Zurla, C., J. Jung, and P. J. Santangelo. "Can we observe changes in mRNA “state”? Overview of methods to study mRNA interactions with regulatory proteins relevant in cancer related processes." Analyst 141, no. 2 (2016): 548–62. http://dx.doi.org/10.1039/c5an01959a.

Full text

Abstract:

RNA binding proteins (RBP) regulate the editing, localization, stabilization, translation, and degradation of ribonucleic acids (RNA) through their interactions with specificcis-acting elements within target RNAs.

APA, Harvard, Vancouver, ISO, and other styles

18

Muench, Douglas G., and Nam-Il Park. "Messages on the move: the role of the cytoskeleton in mRNA localization and translation in plant cellsThis review is one of a selection of papers published in the Special Issue on Plant Cell Biology." Canadian Journal of Botany 84, no. 4 (April 2006): 572–80. http://dx.doi.org/10.1139/b05-167.

Full text

Abstract:

The cytoskeleton plays an important role in numerous cellular processes, including subcellular mRNA localization and translation. Several examples of mRNA localization have emerged in plant cells, and these appear to function in protein targeting, the establishment of polarity, and cell-to-cell trafficking. The identification of several cytoskeleton-associated RNA-binding proteins in plant cells has made available candidate proteins that mediate the interaction between mRNA and the cytoskeleton, and possibly play a role in mRNA localization and translational control. We propose a model that links mRNA–microtubule interactions to translational autoregulation, a process that may assist in the efficient and regulated binding of proteins to microtubules.

APA, Harvard, Vancouver, ISO, and other styles

19

Fastenau, Caitlyn, Helen Cifuentes, Grant Kauwe, and Tara Tracy. "THE ROLE OF CAPRIN-1 PROTEIN DYSREGULATION IN SYNAPSE DECLINE LEADING TO PROGRESSION OF TAUOPATHIES." Innovation in Aging 3, Supplement_1 (November 2019): S835—S836. http://dx.doi.org/10.1093/geroni/igz038.3078.

Full text

Abstract:

Abstract Many neurodegenerative diseases are characterized by accumulation of proteins such as tau, a microtubule stabilization protein. Toxic tau forms tangles and affects neuronal synapse function, an early step of neurodegeneration. To focus on synapse function, we highlighted Caprin-1 protein. Through gene ontology, Caprin-1 is related to RNA granule proteins, important for transport and local translation in dendrites. Caprin-1 is of interest for neurodegeneration because it is a memory related protein, transports mRNA in RNA granules, and knock out mice demonstrate memory deficits. As we age, the performance of local translation in the dendrites is compromised and leads to synapse dysfunction. We hypothesize Caprin-1 binds to Tau and becomes disrupted. This leads to the dissolution of RNA granules, inhibition of mRNA transport in dendrites, suppression of translation, and failure of synapse. Early western blot data showed reduced Caprin-1 in PS19 Tau+, supporting our model that Caprin-1 is disrupted in disease models. Through immunohistochemistry, we investigated the localization of Caprin-1 in the mouse hippocampus. We observed Caprin-1 localization to dendrites of CA1 neurons in the hippocampus. Furthermore, Caprin-1 exhibited colocalization with Rps6, an RNA granule marker. This suggests Caprin-1 associates with RNA granules in mouse hippocampus. Finally, we investigated the localization of Caprin-1 in human iPSC-derived neurons. Similar to the mouse hippocampus, we observed localization of Caprin-1 to dendrites of human neurons. In future directions, we will examine whether pathogenic tau alters the association of Caprin-1 with RNA granules and the mechanisms by which pathogenic tau negatively effects synapse function.

APA, Harvard, Vancouver, ISO, and other styles

20

Toki, Naoko, Hazuki Takahashi, Harshita Sharma, Matthew N. Z. Valentine, Ferdous-Ur M. Rahman, Silvia Zucchelli, Stefano Gustincich, and Piero Carninci. "SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies." Nucleic Acids Research 48, no. 20 (November 2, 2020): 11626–44. http://dx.doi.org/10.1093/nar/gkaa814.

Full text

Abstract:

Abstract SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.

APA, Harvard, Vancouver, ISO, and other styles

21

Child, Jessica R., Qiang Chen, David W. Reid, Sujatha Jagannathan, and Christopher V. Nicchitta. "Recruitment of endoplasmic reticulum-targeted and cytosolic mRNAs into membrane-associated stress granules." RNA 27, no. 10 (July 8, 2021): 1241–56. http://dx.doi.org/10.1261/rna.078858.121.

Full text

Abstract:

Stress granules (SGs) are membraneless organelles composed of mRNAs and RNA binding proteins which undergo assembly in response to stress-induced inactivation of translation initiation. In general, SG recruitment is limited to a subpopulation of a given mRNA species and RNA-seq analyses of purified SGs revealed that signal sequence-encoding (i.e., endoplasmic reticulum [ER]-targeted) transcripts are significantly underrepresented, consistent with prior reports that ER localization can protect mRNAs from SG recruitment. Using translational profiling, cell fractionation, and single molecule mRNA imaging, we examined SG biogenesis following activation of the unfolded protein response (UPR) by 1,4-dithiothreitol (DTT) and report that gene-specific subsets of cytosolic and ER-targeted mRNAs can be recruited into SGs. Furthermore, we demonstrate that SGs form in close proximity to or directly associated with the ER membrane. ER-associated SG assembly was also observed during arsenite stress, suggesting broad roles for the ER in SG biogenesis. Recruitment of a given mRNA into SGs required stress-induced translational repression, though translational inhibition was not solely predictive of an mRNA's propensity for SG recruitment. SG formation was prevented by the transcriptional inhibitors actinomycin D or triptolide, suggesting a functional link between gene transcriptional state and SG biogenesis. Collectively these data demonstrate that ER-targeted and cytosolic mRNAs can be recruited into ER-associated SGs and this recruitment is sensitive to transcriptional inhibition. We propose that newly transcribed mRNAs exported under conditions of suppressed translation initiation are primary SG substrates, with the ER serving as the central subcellular site of SG formation.

APA, Harvard, Vancouver, ISO, and other styles

22

Reznik, Boris, and Jens Lykke-Andersen. "Regulated and quality-control mRNA turnover pathways in eukaryotes." Biochemical Society Transactions 38, no. 6 (November 24, 2010): 1506–10. http://dx.doi.org/10.1042/bst0381506.

Full text

Abstract:

Gene expression can be regulated at multiple levels, including transcription, RNA processing, RNA localization, translation and, finally, RNA turnover. RNA degradation may occur at points along the processing pathway or during translation as it undergoes quality control by RNA surveillance systems. Alternatively, mRNAs may be subject to regulated degradation, often mediated by cis-encoded determinants in the mRNA sequence that, through the recruitment of trans factors, determine the fate of the mRNA. The aim of the present review is to highlight mechanisms of regulated and quality-control RNA degradation in eukaryotic cells, with an emphasis on mammals.

APA, Harvard, Vancouver, ISO, and other styles

23

Ji, Yingbiao, and Alexei V. Tulin. "Poly(ADP-Ribosyl)ation of hnRNP A1 Protein Controls Translational Repression in Drosophila." Molecular and Cellular Biology 36, no. 19 (July 11, 2016): 2476–86. http://dx.doi.org/10.1128/mcb.00207-16.

Full text

Abstract:

Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) regulates the posttranscriptional fate of RNA during development.DrosophilahnRNP A1, Hrp38, is required for germ line stem cell maintenance and oocyte localization. The mRNA targets regulated by Hrp38 are mostly unknown. We identified 428 Hrp38-associated gene transcripts in the fly ovary, including mRNA of the translational repressor Nanos. We found that Hrp38 binds to the 3′ untranslated region (UTR) of Nanos mRNA, which contains a translation control element. We have demonstrated that translation of the luciferase reporter bearing the Nanos 3′ UTR is enhanced by dsRNA-mediated Hrp38 knockdown as well as by mutating potential Hrp38-binding sites. Our data show that poly(ADP-ribosyl)ation inhibits Hrp38 binding to the Nanos 3′ UTR, increasing the translationin vivoandin vitro.hrp38andPargnull mutants showed an increased ectopic Nanos translation early in the embryo. We conclude that Hrp38 represses Nanos translation, whereas its poly(ADP-ribosyl)ation relieves the repression effect, allowing restricted Nanos expression in the posterior germ plasm during oogenesis and early embryogenesis.

APA, Harvard, Vancouver, ISO, and other styles

24

Ohashi and Shiina. "Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules." Biomolecules 10, no. 2 (January 22, 2020): 167. http://dx.doi.org/10.3390/biom10020167.

Full text

Abstract:

Spatiotemporal translational regulation plays a key role in determining cell fate and function. Specifically, in neurons, local translation in dendrites is essential for synaptic plasticity and long-term memory formation. To achieve local translation, RNA-binding proteins in RNA granules regulate target mRNA stability, localization, and translation. To date, mRNAs localized to dendrites have been identified by comprehensive analyses. In addition, mRNAs associated with and regulated by RNA-binding proteins have been identified using various methods in many studies. However, the results obtained from these numerous studies have not been compiled together. In this review, we have catalogued mRNAs that are localized to dendrites and are associated with and regulated by the RNA-binding proteins fragile X mental retardation protein (FMRP), RNA granule protein 105 (RNG105, also known as Caprin1), Ras-GAP SH3 domain binding protein (G3BP), cytoplasmic polyadenylation element binding protein 1 (CPEB1), and staufen double-stranded RNA binding proteins 1 and 2 (Stau1 and Stau2) in RNA granules. This review provides comprehensive information on dendritic mRNAs, the neuronal functions of mRNA-encoded proteins, the association of dendritic mRNAs with RNA-binding proteins in RNA granules, and the effects of RNA-binding proteins on mRNA regulation. These findings provide insights into the mechanistic basis of protein-synthesis-dependent synaptic plasticity and memory formation and contribute to future efforts to understand the physiological implications of local regulation of dendritic mRNAs in neurons.

APA, Harvard, Vancouver, ISO, and other styles

25

Lee, K., M. A. Fajardo, and R. E. Braun. "A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor." Molecular and Cellular Biology 16, no. 6 (June 1996): 3023–34. http://dx.doi.org/10.1128/mcb.16.6.3023.

Full text

Abstract:

Translation of the mouse protamine 1 (Prm-1) mRNA is repressed for several days during male germ cell differentiation. With the hope of cloning genes that regulate the translational repression of Prm-1, we screened male germ cell cDNA expression libraries with the 3' untranslated region of the Prm-1 RNA. From this screen we obtained two independent clones that encode Prbp, a Prm-1 RNA-binding protein. Prbp contains two copies of a double-stranded-RNA-binding domain. In vitro, the protein binds to a portion of the Prm-1 3' untranslated region previously shown to be sufficient for translational repression in transgenic mice, as well as to poly(I). poly(C). Prbp protein is present in multiple forms in cytoplasmic extracts prepared from wild-type mouse testes and is absent from testes of germ cell-deficient mouse mutants, suggesting that Prbp is restricted to the germ cells of the testis. Immunocytochemical localization confirmed that Prbp is present in the cytoplasmic compartment of late-stage meiotic cells and haploid round spermatids. Recombinant Prbp protein inhibits the translation of multiple mRNAs in a wheat germ lysate, suggesting that Prbp acts to repress translation in round spermatids. While this protein lacks complete specificity for Prm-1-containing RNAs in vitro, the properties of Prbp are consistent with it acting as a general repressor of translation.

APA, Harvard, Vancouver, ISO, and other styles

26

Jansova, Denisa, Anna Tetkova, Marketa Koncicka, Michal Kubelka, and Andrej Susor. "Localization of RNA and translation in the mammalian oocyte and embryo." PLOS ONE 13, no. 3 (March 12, 2018): e0192544. http://dx.doi.org/10.1371/journal.pone.0192544.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Chouaib, Racha, Adham Safieddine, Xavier Pichon, Arthur Imbert, Oh Sung Kwon, Aubin Samacoits, Abdel-Meneem Traboulsi, et al. "A Dual Protein-mRNA Localization Screen Reveals Compartmentalized Translation and Widespread Co-translational RNA Targeting." Developmental Cell 54, no. 6 (September 2020): 773–91. http://dx.doi.org/10.1016/j.devcel.2020.07.010.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

van Eeden, Fredericus J. M., Isabel M. Palacios, Mark Petronczki, Matthew J. D. Weston, and Daniel St Johnston. "Barentsz is essential for the posterior localization of oskar mRNA and colocalizes with it to the posterior pole." Journal of Cell Biology 154, no. 3 (July 30, 2001): 511–24. http://dx.doi.org/10.1083/jcb.200105056.

Full text

Abstract:

The localization of Oskar at the posterior pole of the Drosophila oocyte induces the assembly of the pole plasm and therefore defines where the abdomen and germ cells form in the embryo. This localization is achieved by the targeting of oskar mRNA to the posterior and the localized activation of its translation. oskar mRNA seems likely to be actively transported along microtubules, since its localization requires both an intact microtubule cytoskeleton and the plus end–directed motor kinesin I, but nothing is known about how the RNA is coupled to the motor. Here, we describe barentsz, a novel gene required for the localization of oskar mRNA. In contrast to all other mutations that disrupt this process, barentsz-null mutants completely block the posterior localization of oskar mRNA without affecting bicoid and gurken mRNA localization, the organization of the microtubules, or subsequent steps in pole plasm assembly. Surprisingly, most mutant embryos still form an abdomen, indicating that oskar mRNA localization is partially redundant with the translational control. Barentsz protein colocalizes to the posterior with oskar mRNA, and this localization is oskar mRNA dependent. Thus, Barentsz is essential for the posterior localization of oskar mRNA and behaves as a specific component of the oskar RNA transport complex.

APA, Harvard, Vancouver, ISO, and other styles

29

Isoyama, Takeshi, Nobuhiko Kamoshita, Kotaro Yasui, Atsushi Iwai, Kazuko Shiroki, Haruka Toyoda, Akio Yamada, Yoshinari Takasaki, and Akio Nomoto. "Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than on poliovirus RNA." Journal of General Virology 80, no. 9 (September 1, 1999): 2319–27. http://dx.doi.org/10.1099/0022-1317-80-9-2319.

Full text

Abstract:

Translation initiation of poliovirus and hepatitis C virus (HCV) RNA occurs by entry of ribosomes to the internal RNA sequence, called the internal ribosomal entry site (IRES). Both IRES bind to the La protein and are thought to require the protein for their translation initiation activity, although they are greatly different in both the primary and predicted secondary structures. To compare the La protein requirement for these IRES, we took advantage of I-RNA from the yeast Saccharomyces cerevisiae, which has been reported to bind to La protein and block poliovirus IRES-mediated translation initiation. In a cell-free translation system prepared from HeLa cells, yeast I-RNA inhibited translation initiation on poliovirus RNA as expected, but did not significantly inhibit translation initiation on HCV RNA. However, the translation initiation directed by either IRES was apparently inhibited by I-RNA in rabbit reticulocyte lysates, in which La protein is limiting. I-RNA-mediated inhibition of HCV IRES-dependent translation in rabbit reticulocyte lysates was reversed by exogenous addition of purified recombinant La protein of smaller amounts than necessary to reverse poliovirus IRES-dependent translation. These results suggest that HCV IRES requires lower concentrations of La protein for its function than does poliovirus IRES. Immunofluorescence studies showed that HCV infection appeared not to affect the subcellular localization of La protein, which exists mainly in the nucleus, although La protein redistributed to the cytoplasm after poliovirus infection. The data are compatible with the low requirement of La protein for HCV IRES activity.

APA, Harvard, Vancouver, ISO, and other styles

30

Makeeva, Desislava S., Claire L. Riggs, Anton V. Burakov, Pavel A. Ivanov, Artem S. Kushchenko, Dmitri A. Bykov, Vladimir I. Popenko, Vladimir S. Prassolov, Pavel V. Ivanov, and Sergey E. Dmitriev. "Relocalization of Translation Termination and Ribosome Recycling Factors to Stress Granules Coincides with Elevated Stop-Codon Readthrough and Reinitiation Rates upon Oxidative Stress." Cells 12, no. 2 (January 8, 2023): 259. http://dx.doi.org/10.3390/cells12020259.

Full text

Abstract:

Upon oxidative stress, mammalian cells rapidly reprogram their translation. This is accompanied by the formation of stress granules (SGs), cytoplasmic ribonucleoprotein condensates containing untranslated mRNA molecules, RNA-binding proteins, 40S ribosomal subunits, and a set of translation initiation factors. Here we show that arsenite-induced stress causes a dramatic increase in the stop-codon readthrough rate and significantly elevates translation reinitiation levels on uORF-containing and bicistronic mRNAs. We also report the recruitment of translation termination factors eRF1 and eRF3, as well as ribosome recycling and translation reinitiation factors ABCE1, eIF2D, MCT-1, and DENR to SGs upon arsenite treatment. Localization of these factors to SGs may contribute to a rapid resumption of mRNA translation after stress relief and SG disassembly. It may also suggest the presence of post-termination, recycling, or reinitiation complexes in SGs. This new layer of translational control under stress conditions, relying on the altered spatial distribution of translation factors between cellular compartments, is discussed.

APA, Harvard, Vancouver, ISO, and other styles

31

Peculis, B. A., and J. G. Gall. "Localization of the nucleolar protein NO38 in amphibian oocytes." Journal of Cell Biology 116, no. 1 (January 1, 1992): 1–14. http://dx.doi.org/10.1083/jcb.116.1.1.

Full text

Abstract:

To examine the role of primary amino acid sequence in the localization of proteins within the nucleus, we studied the nucleolar protein NO38 of amphibian oocytes. We synthesized NO38 transcripts in vitro, injected them into the oocyte cytoplasm, and followed the distribution of the translation products. The injected RNA contained a short sequence encoding an epitope derived from the human c-myc protein. We used an mAb against this epitope to detect translation products from injected RNAs by Western blots and by immunofluoresent staining of cytological preparations. When full-length transcripts of NO38 were injected into oocytes, the translation products accumulated efficiently in the germinal vesicle, and a major fraction was localized in the multiple nucleoli. To identify protein domains involved in this nucleolus-specific accumulation, we prepared a series of carboxy-terminal deletions of the cDNA. Oocytes injected with RNA encoding truncated forms of NO38 were examined for altered patterns of protein accumulation. We defined a domain of about 24 amino acids near the carboxy terminus that was essential for nucleolar localization of NO38. This domain is separated by more than 70 amino acids from two putative nuclear localization signals near the middle of the molecule. Hybrid constructs were made which encoded part of Escherichia coli beta-galactosidase or pyruvate kinase fused to a long segment of NO38 containing the essential domain. Injection of RNA from these constructs showed that the essential domain was not sufficient to target the hybrid proteins to the nucleolus. We suggest that nucleolar accumulation of NO38 requires more than a single linear domain.

APA, Harvard, Vancouver, ISO, and other styles

32

Nakamura, Akira, Reiko Amikura, Kazuko Hanyu, and Satoru Kobayashi. "Me31B silences translation of oocyte-localizing RNAs through the formation of cytoplasmic RNP complex duringDrosophilaoogenesis." Development 128, no. 17 (September 1, 2001): 3233–42. http://dx.doi.org/10.1242/dev.128.17.3233.

Full text

Abstract:

Embryonic patterning in Drosophila is regulated by maternal factors. Many such factors become localized as mRNAs within the oocyte during oogenesis and are translated in a spatio-temporally regulated manner. These processes are controlled by trans-acting proteins, which bind to the target RNAs to form a ribonucleoprotein (RNP) complex. We report that a DEAD-box protein, Me31B, forms a cytoplasmic RNP complex with oocyte-localizing RNAs and Exuperantia, a protein involved in RNA localization. During early oogenesis, loss of Me31B causes premature translation of oocyte-localizing RNAs within nurse cells, without affecting their transport to the oocyte. These results suggest that Me31B mediates translational silencing of RNAs during their transport to the oocyte. Our data provide evidence that RNA transport and translational control are linked through the assembly of RNP complex.

APA, Harvard, Vancouver, ISO, and other styles

33

Pedder, Christopher M., Dianne Ford, and John E. Hesketh. "Targeting of transcripts encoding membrane proteins in polarized epithelia: RNA–protein binding studies of the SGLT1 3′-UTR." Biochemical Society Transactions 36, no. 3 (May 21, 2008): 525–27. http://dx.doi.org/10.1042/bst0360525.

Full text

Abstract:

mRNA stability, mRNA translation and spatial localization of mRNA species within a cell can be governed by signals in the 3′-UTR (3′-untranslated region). Local translation of proteins is essential for the development of many eukaryotic cell types, such as the Drosophila embryo, where the spatial and temporal localization of bicoid and gurken mRNAs, among others, is required to establish morphogen gradients. More recent studies have suggested that mRNA localization also occurs with transcripts coding for membrane-based or secreted proteins, and that localization at organelles such as the endoplasmic reticulum directs translation more efficiently to specific subdomains, so as to aid correct protein localization. In human epithelial cells, the mRNA coding for SGLT1 (sodium–glucose co-transporter 1), an apical membrane protein, has been shown to be localized apically in polarized cells. However, the nature of the signals and RNA-binding proteins involved are unknown. Ongoing work is aimed at identifying the localization signals in the SGLT1 3′-UTR and the corresponding binding proteins. Using a protein extract from polarized Caco-2 cells, both EMSAs (electrophoretic mobility-shift assays) and UV cross-linking assays have shown that a specific protein complex is formed with the first 300 bases of the 3′-UTR sequence. MFold predictions suggest that this region folds into a complex structure and ongoing studies using a series of strategic deletions are being carried out to identify the precise nature of the motif involved, particularly the role of the sequence or RNA secondary structure, as well as to identify the main proteins present within the complex. Such information will provide details of the post-transcriptional events that lead to apical localization of the SGLT1 transcript and may reveal mechanisms of more fundamental importance in the apical localization of proteins in polarized epithelia.

APA, Harvard, Vancouver, ISO, and other styles

34

Gray, Nicola K., Lenka Hrabálková, Jessica P. Scanlon, and Richard W. P. Smith. "Poly(A)-binding proteins and mRNA localization: who rules the roost?" Biochemical Society Transactions 43, no. 6 (November 27, 2015): 1277–84. http://dx.doi.org/10.1042/bst20150171.

Full text

Abstract:

RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals.

APA, Harvard, Vancouver, ISO, and other styles

35

Kraut-Cohen, Judith, Evgenia Afanasieva, Liora Haim-Vilmovsky, Boris Slobodin, Ido Yosef, Eitan Bibi, and Jeffrey E. Gerst. "Translation- and SRP-independent mRNA targeting to the endoplasmic reticulum in the yeast Saccharomyces cerevisiae." Molecular Biology of the Cell 24, no. 19 (October 2013): 3069–84. http://dx.doi.org/10.1091/mbc.e13-01-0038.

Full text

Abstract:

mRNAs encoding secreted/membrane proteins (mSMPs) are believed to reach the endoplasmic reticulum (ER) in a translation-dependent manner to confer protein translocation. Evidence exists, however, for translation- and signal recognition particle (SRP)–independent mRNA localization to the ER, suggesting that there are alternate paths for RNA delivery. We localized endogenously expressed mSMPs in yeast using an aptamer-based RNA-tagging procedure and fluorescence microscopy. Unlike mRNAs encoding polarity and secretion factors that colocalize with cortical ER at the bud tip, mSMPs and mRNAs encoding soluble, nonsecreted, nonpolarized proteins localized mainly to ER peripheral to the nucleus (nER). Synthetic nontranslatable uracil-rich mRNAs were also demonstrated to colocalize with nER in yeast. This mRNA–ER association was verified by subcellular fractionation and reverse transcription-PCR, single-molecule fluorescence in situ hybridization, and was not inhibited upon SRP inactivation. To better understand mSMP targeting, we examined aptamer-tagged USE1, which encodes a tail-anchored membrane protein, and SUC2, which encodes a soluble secreted enzyme. USE1 and SUC2 mRNA targeting was not abolished by the inhibition of translation or removal of elements involved in translational control. Overall we show that mSMP targeting to the ER is both translation- and SRP-independent, and regulated by cis elements contained within the message and trans-acting RNA-binding proteins (e.g., She2, Puf2).

APA, Harvard, Vancouver, ISO, and other styles

36

Jansova, Denisa, Daria Aleshkina, Anna Jindrova, Rajan Iyyappan, Qin An, Guoping Fan, and Andrej Susor. "Single Molecule RNA Localization and Translation in the Mammalian Oocyte and Embryo." Journal of Molecular Biology 433, no. 19 (September 2021): 167166. http://dx.doi.org/10.1016/j.jmb.2021.167166.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Yasuda, Kyota, Huaye Zhang, David Loiselle, Timothy Haystead, Ian G. Macara, and Stavroula Mili. "The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules." Journal of Cell Biology 203, no. 5 (December 2, 2013): 737–46. http://dx.doi.org/10.1083/jcb.201306058.

Full text

Abstract:

RNA localization pathways direct numerous mRNAs to distinct subcellular regions and affect many physiological processes. In one such pathway the tumor-suppressor protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions, forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. Labeling of newly synthesized proteins revealed that Fus promotes translation preferentially within protrusions. Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules. We show that overexpression or mutation of Fus results in formation of granules, which preferentially recruit APC-RNPs. Remarkably, these granules are not translationally silent. Instead, APC-RNP transcripts are translated within cytoplasmic Fus granules. These results unexpectedly show that translation can occur within stress-like granules. Importantly, they identify a new local function for cytoplasmic Fus with implications for ALS pathology.

APA, Harvard, Vancouver, ISO, and other styles

38

Blanco-Urrejola, Maite, Adhara Gaminde-Blasco, María Gamarra, Aida de la Cruz, Elena Vecino, Elena Alberdi, and Jimena Baleriola. "RNA Localization and Local Translation in Glia in Neurological and Neurodegenerative Diseases: Lessons from Neurons." Cells 10, no. 3 (March 12, 2021): 632. http://dx.doi.org/10.3390/cells10030632.

Full text

Abstract:

Cell polarity is crucial for almost every cell in our body to establish distinct structural and functional domains. Polarized cells have an asymmetrical morphology and therefore their proteins need to be asymmetrically distributed to support their function. Subcellular protein distribution is typically achieved by localization peptides within the protein sequence. However, protein delivery to distinct cellular compartments can rely, not only on the transport of the protein itself but also on the transport of the mRNA that is then translated at target sites. This phenomenon is known as local protein synthesis. Local protein synthesis relies on the transport of mRNAs to subcellular domains and their translation to proteins at target sites by the also localized translation machinery. Neurons and glia specially depend upon the accurate subcellular distribution of their proteome to fulfil their polarized functions. In this sense, local protein synthesis has revealed itself as a crucial mechanism that regulates proper protein homeostasis in subcellular compartments. Thus, deregulation of mRNA transport and/or of localized translation can lead to neurological and neurodegenerative diseases. Local translation has been more extensively studied in neurons than in glia. In this review article, we will summarize the state-of-the art research on local protein synthesis in neuronal function and dysfunction, and we will discuss the possibility that local translation in glia and deregulation thereof contributes to neurological and neurodegenerative diseases.

APA, Harvard, Vancouver, ISO, and other styles

39

Garin, Shahar, Ofri Levi, Bar Cohen, Adi Golani-Armon, and Yoav S. Arava. "Localization and RNA Binding of Mitochondrial Aminoacyl tRNA Synthetases." Genes 11, no. 10 (October 12, 2020): 1185. http://dx.doi.org/10.3390/genes11101185.

Full text

Abstract:

Mitochondria contain a complete translation machinery that is used to translate its internally transcribed mRNAs. This machinery uses a distinct set of tRNAs that are charged with cognate amino acids inside the organelle. Interestingly, charging is executed by aminoacyl tRNA synthetases (aaRS) that are encoded by the nuclear genome, translated in the cytosol, and need to be imported into the mitochondria. Here, we review import mechanisms of these enzymes with emphasis on those that are localized to both mitochondria and cytosol. Furthermore, we describe RNA recognition features of these enzymes and their interaction with tRNA and non-tRNA molecules. The dual localization of mitochondria-destined aaRSs and their association with various RNA types impose diverse impacts on cellular physiology. Yet, the breadth and significance of these functions are not fully resolved. We highlight here possibilities for future explorations.

APA, Harvard, Vancouver, ISO, and other styles

40

Gao, Yuanhui, Hui Cao, Denggao Huang, Linlin Zheng, Zhenyu Nie, and Shufang Zhang. "RNA-Binding Proteins in Bladder Cancer." Cancers 15, no. 4 (February 10, 2023): 1150. http://dx.doi.org/10.3390/cancers15041150.

Full text

Abstract:

RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance. Uncovering the regulatory mechanisms of RBPs in bladder cancer is aimed at addressing the occurrence and progression of bladder cancer and finding new therapies for cancer treatment. This article reviews the effects and mechanisms of several RBPs on bladder cancer and summarizes the different types of RBPs involved in the progression of bladder cancer and the potential molecular mechanisms by which they are regulated, with a view to providing information for basic and clinical researchers.

APA, Harvard, Vancouver, ISO, and other styles

41

Evans Bergsten, S., T. Huang, S. Chatterjee, and E. R. Gavis. "Recognition and long-range interactions of a minimal nanos RNA localization signal element." Development 128, no. 3 (February 1, 2001): 427–35. http://dx.doi.org/10.1242/dev.128.3.427.

Full text

Abstract:

Localization of nanos (nos) mRNA to the germ plasm at the posterior pole of the Drosophila embryo is essential to activate nos translation and thereby generate abdominal segments. nos RNA localization is mediated by a large cis-acting localization signal composed of multiple, partially redundant elements within the nos 3′ untranslated region. We identify a protein of approximately 75 kDa (p75) that interacts specifically with the nos +2′ localization signal element. We show that the function of this element can be delimited to a 41 nucleotide domain that is conserved between D. melanogaster and D. virilis, and confers near wild-type localization when present in three copies. Two small mutations within this domain eliminate both +2′ element localization function and p75 binding, consistent with a role for p75 in nos RNA localization. In the intact localization signal, the +2′ element collaborates with adjacent localization elements. We show that different +2′ element mutations not only abolish collaboration between the +2′ and adjacent +1 element but also produce long-range deleterious effects on localization signal function. Our results suggest that higher order structural interactions within the localization signal, which requires factors such as p75, are necessary for association of nos mRNA with the germ plasm.

APA, Harvard, Vancouver, ISO, and other styles

42

Lie, Y. S., and P. M. Macdonald. "Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation." Development 126, no. 6 (March 15, 1999): 1129–38. http://dx.doi.org/10.1242/dev.126.6.1129.

Full text

Abstract:

The product of the oskar gene directs posterior patterning in the Drosophila oocyte, where it must be deployed specifically at the posterior pole. Proper expression relies on the coordinated localization and translational control of the oskar mRNA. Translational repression prior to localization of the transcript is mediated, in part, by the Bruno protein, which binds to discrete sites in the 3′ untranslated region of the oskar mRNA. To begin to understand how Bruno acts in translational repression, we performed a yeast two-hybrid screen to identify Bruno-interacting proteins. One interactor, described here, is the product of the apontic gene. Coimmunoprecipitation experiments lend biochemical support to the idea that Bruno and Apontic proteins physically interact in Drosophila. Genetic experiments using mutants defective in apontic and bruno reveal a functional interaction between these genes. Given this interaction, Apontic is likely to act together with Bruno in translational repression of oskar mRNA. Interestingly, Apontic, like Bruno, is an RNA-binding protein and specifically binds certain regions of the oskar mRNA 3′ untranslated region.

APA, Harvard, Vancouver, ISO, and other styles

43

Kashida, Shunnichi, Dan Ohtan Wang, Hirohide Saito, and Zoher Gueroui. "Nanoparticle-based local translation reveals mRNA as a translation-coupled scaffold with anchoring function." Proceedings of the National Academy of Sciences 116, no. 27 (June 19, 2019): 13346–51. http://dx.doi.org/10.1073/pnas.1900310116.

Full text

Abstract:

The spatial regulation of messenger RNA (mRNA) translation is central to cellular functions and relies on numerous complex processes. Biomimetic approaches could bypass these endogenous complex processes, improve our comprehension of the regulation, and allow for controlling local translation regulations and functions. However, the causality between local translation and nascent protein function remains elusive. Here, we developed a nanoparticle (NP)-based strategy to magnetically control mRNA spatial patterns in mammalian cell extracts and investigate how local translation impacts nascent protein localization and function. By monitoring the translation of the magnetically localized mRNAs, we show that mRNA–NP complexes operate as a source for the continuous production of proteins from defined positions. By applying this approach to actin-binding proteins, we triggered the local formation of actin cytoskeletons and identified the minimal requirements for spatial control of the actin filament network. In addition, our bottom-up approach identified a role for mRNA as a translation-coupled scaffold for the function of nascent N-terminal protein domains. Our approach will serve as a platform for regulating mRNA localization and investigating the function of nascent protein domains during translation.

APA, Harvard, Vancouver, ISO, and other styles

44

Sawicka, Kirsty, Martin Bushell, Keith A. Spriggs, and Anne E. Willis. "Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein." Biochemical Society Transactions 36, no. 4 (July 22, 2008): 641–47. http://dx.doi.org/10.1042/bst0360641.

Full text

Abstract:

PTB (polypyrimidine-tract-binding protein) is a ubiquitous RNA-binding protein. It was originally identified as a protein with a role in splicing but it is now known to function in a large number of diverse cellular processes including polyadenylation, mRNA stability and translation initiation. Specificity of PTB function is achieved by a combination of changes in the cellular localization of this protein (its ability to shuttle from the nucleus to the cytoplasm is tightly controlled) and its interaction with additional proteins. These differences in location and trans-acting factor requirements account for the fact that PTB acts both as a suppressor of splicing and an activator of translation. In the latter case, the role of PTB in translation has been studied extensively and it appears that this protein is required for an alternative form of translation initiation that is mediated by a large RNA structural element termed an IRES (internal ribosome entry site) that allows the synthesis of picornaviral proteins and cellular proteins that function to control cell growth and cell death. In the present review, we discuss how PTB regulates these disparate processes.

APA, Harvard, Vancouver, ISO, and other styles

45

Saffman, Emma E., Sylvia Styhler, Katherine Rother, Weihua Li, Stéphane Richard, and Paul Lasko. "Premature Translation of oskar in Oocytes Lacking the RNA-Binding Protein Bicaudal-C." Molecular and Cellular Biology 18, no. 8 (August 1, 1998): 4855–62. http://dx.doi.org/10.1128/mcb.18.8.4855.

Full text

Abstract:

ABSTRACT Bicaudal-C (Bic-C) is required duringDrosophila melanogaster oogenesis for several processes, including anterior-posterior patterning. The gene encodes a protein with five copies of the KH domain, a motif found in a number of RNA-binding proteins. Using antibodies raised against the BIC-C protein, we show that multiple isoforms of the protein exist in ovaries and that the protein, like the RNA, accumulates in the developing oocyte early in oogenesis. BIC-C protein expressed in mammalian cells can bind RNA in vitro, and a point mutation in one of the KH domains that causes a strong Bic-C phenotype weakens this binding. In addition, oskar translation commences prior to posterior localization of oskar RNA inBic-C − oocytes, indicating thatBic-C may regulate oskar translation during oogenesis.

APA, Harvard, Vancouver, ISO, and other styles

46

Shi, Yijiang, Joseph Gera, and Alan Lichtenstein. "Interleukin-6 (IL-6) Enhances C-MYC Translation IN MULTIPLE MYELOMA (MM) CELLS: ROLE of IL-6-INDUCED EFFECTS On the C-MYC RNA-Binding PROTEIN, HNRNPA1." Blood 114, no. 22 (November 20, 2009): 3839. http://dx.doi.org/10.1182/blood.v114.22.3839.3839.

Full text

Abstract:

Abstract Abstract 3839 Poster Board III-775 Our previous work (Cancer Research 68:10215, 2008) demonstrated that IL-6 enhanced c-myc protein expression in MM cells and function of the RNA-binding protein, hnRNPA1 (A1), was required. This occurred by way of enhanced cap-independent translation mediated via the internal ribosome entry site (IRES) in the 5'UTR of the myc RNA. IRES-dependent translation is the fail safe mechanism for protein expression when cap-dependent translation is suppressed by mTOR inhibition (with curtailed RNA cap-ribosome binding) and is especially important when an mRNA leader is relatively long and highly structured, such that scanning ribosomes are unlikely to efficiently initiate translation. The IRES directly recruits the ribosome to within close proximity to the start codon, bypassing the need for cap binding and ribosome scanning. HNRNPA1 (A1) is a documented IRES trans-acting factor (ITAF) for the myc IRES, facilitating translation but how its effects are enhanced by IL-6 is unknown. HNRNPA1 is a shuttling protein which binds the myc RNA in the nucleus and transports it to the cytoplasm. Initial experiments demonstrated that IL-6 stimulation of ANBL-6 and OCI-My5 MM cell lines, as well as several primary MM specimens, significantly increased the cytoplasmic localization of A1. To test if this enhanced cytoplasmic localization was critical, we stably expressed a dominant negative (DN) A1 gene that is incapable of nuclear-to-cytoplasmic shuttling and which also prevents endogenous hnRNPA1 shuttling. The DN also prevented A1-mediated transport of the shuttling protein, FUS. Expression of the DN in ANBL-6 cells prevented IL-6-induced effects on myc expression and on ANBL-6 cell growth. We also tested if IL-6 treatment affected A1 binding to the myc RNA by immunoprecipitating A1 and performing real time PCR on the immunoprecipitate for myc RNA levels. A significant increase in A1-myc RNA binding was confirmed. Mass spectroscopy demonstrated that IL-6 induced phosphorylation of A1 in its RNA-binding domain, which possibly mediated the enhanced binding. These results demonstrate that, by enhanced binding of the myc ITAF, hnRNPA1, to the myc IRES, and by enhanced transport of the complex to the translationally active cytoplasmic subcellular site, IL-6 may stimulate c-myc translation and subsequent MM cell growth. Disclosures: No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

47

Fernández-Moya, Sandra M., Janina Ehses, Karl E. Bauer, Rico Schieweck, Anob M. Chakrabarti, Flora C. Y. Lee, Christin Illig, et al. "RGS4 RNA Secondary Structure Mediates Staufen2 RNP Assembly in Neurons." International Journal of Molecular Sciences 22, no. 23 (December 1, 2021): 13021. http://dx.doi.org/10.3390/ijms222313021.

Full text

Abstract:

RNA-binding proteins (RBPs) act as posttranscriptional regulators controlling the fate of target mRNAs. Unraveling how RNAs are recognized by RBPs and in turn are assembled into neuronal RNA granules is therefore key to understanding the underlying mechanism. While RNA sequence elements have been extensively characterized, the functional impact of RNA secondary structures is only recently being explored. Here, we show that Staufen2 binds complex, long-ranged RNA hairpins in the 3′-untranslated region (UTR) of its targets. These structures are involved in the assembly of Staufen2 into RNA granules. Furthermore, we provide direct evidence that a defined Rgs4 RNA duplex regulates Staufen2-dependent RNA localization to distal dendrites. Importantly, disrupting the RNA hairpin impairs the observed effects. Finally, we show that these secondary structures differently affect protein expression in neurons. In conclusion, our data reveal the importance of RNA secondary structure in regulating RNA granule assembly, localization and eventually translation. It is therefore tempting to speculate that secondary structures represent an important code for cells to control the intracellular fate of their mRNAs.

APA, Harvard, Vancouver, ISO, and other styles

48

Islam, Shabana, Robert K. Montgomery, John J. Fialkovich, and Richard J. Grand. "Developmental and Regional Expression and Localization of mRNAs Encoding Proteins Involved in RNA Translocation." Journal of Histochemistry & Cytochemistry 53, no. 12 (June 27, 2005): 1501–9. http://dx.doi.org/10.1369/jhc.5a6655.2005.

Full text

Abstract:

RNA localization is a regulated component of gene expression of fundamental importance in development and differentiation. Several RNA binding proteins involved in RNA localization during development in Drosophila have been identified, of which Y14, Mago, Pumilio, and IMP-1 are known to be expressed in adult mammalian intestine. The present study was undertaken to define the developmental and regional expression of these proteins, as well as Staufen-1, in mouse intestinal cells and in other tissues and cell lines using RT-PCR, and localization using in situ hybridization and immunohistochemistry. Staufen-1, Y14, Mago-m, and Pumilio-1 were expressed in intestinal epithelial cells of both villus and crypt and in Caco-2 and IEC-6 cells. In contrast, expression of IMP-1 was age- and region-specific, showing clear expression in distal fetal and newborn intestine, but very low or no expression in adult. The mRNAs were cytosolic, with more apical than basal expression in enterocytes. Staufen protein showed a similar localization pattern to that of its cognate mRNA. Overall, the data suggest an essential role for these proteins in intestinal cells. Age and regional expression of IMP-1 may indicate a role in regulation of site-specific translation of intestinal genes or in RNA localization.

APA, Harvard, Vancouver, ISO, and other styles

49

Nicchitta, Christopher V., Rachel S. Lerner, Samuel B. Stephens, Rebecca D. Dodd, and Brook Pyhtila. "Pathways for compartmentalizing protein synthesis in eukaryotic cells: the template-partitioning model." Biochemistry and Cell Biology 83, no. 6 (December 1, 2005): 687–95. http://dx.doi.org/10.1139/o05-147.

Full text

Abstract:

mRNAs encoding signal sequences are translated on endoplasmic reticulum (ER) - bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on cytosolic ribosomes. The partitioning of mRNAs to the ER occurs by positive selection; cytosolic ribosomes engaged in the translation of signal-sequence-bearing proteins are engaged by the signal-recognition particle (SRP) pathway and subsequently trafficked to the ER. Studies have demonstrated that, in addition to the SRP pathway, mRNAs encoding cytosolic proteins can also be partitioned to the ER, suggesting that RNA partitioning in the eukaryotic cell is a complex process requiring the activity of multiple RNA-partitioning pathways. In this review, key findings on this topic are discussed, and the template-partitioning model, describing a hypothetical mechanism for RNA partitioning in the eukaryotic cell, is proposed.Key words: mRNA, ribosome, endoplasmic reticulum, translation, protein synthesis, signal sequence, RNA localization.

APA, Harvard, Vancouver, ISO, and other styles

50

Markussen, F. H., A. M. Michon, W. Breitwieser, and A. Ephrussi. "Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly." Development 121, no. 11 (November 1, 1995): 3723–32. http://dx.doi.org/10.1242/dev.121.11.3723.

Full text

Abstract:

At the posterior pole of the Drosophila oocyte, oskar induces a tightly localized assembly of pole plasm. This spatial restriction of oskar activity has been thought to be achieved by the localization of oskar mRNA, since mislocalization of the RNA to the anterior induces anterior pole plasm. However, ectopic pole plasm does not form in mutant ovaries where oskar mRNA is not localized, suggesting that the unlocalized mRNA is inactive. As a first step towards understanding how oskar activity is restricted to the posterior pole, we analyzed oskar translation in wild type and mutants. We show that the targeting of oskar activity to the posterior pole involves two steps of spatial restriction, cytoskeleton-dependent localization of the mRNA and localization-dependent translation. Furthermore, our experiments demonstrate that two isoforms of Oskar protein are produced by alternative start codon usage. The short isoform, which is translated from the second in-frame AUG of the mRNA, has full oskar activity. Finally, we show that when oskar RNA is localized, accumulation of Oskar protein requires the functions of vasa and tudor, as well as oskar itself, suggesting a positive feedback mechanism in the induction of pole plasm by oskar.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'RNA localization and translation'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles