Journal articles: 'Granules RNP'

1

Krüger, Timothy, Mario Hofweber, and Susanne Kramer. "SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains." Molecular Biology of the Cell 24, no. 13 (July 2013): 2098–111. http://dx.doi.org/10.1091/mbc.e13-01-0068.

Full text

Abstract:

Ribonucleoprotein (RNP) granules are cytoplasmic, microscopically visible structures composed of RNA and protein with proposed functions in mRNA decay and storage. Trypanosomes have several types of RNP granules, but lack most of the granule core components identified in yeast and humans. The exception is SCD6/Rap55, which is essential for processing body (P-body) formation. In this study, we analyzed the role of trypanosome SCD6 in RNP granule formation. Upon overexpression, the majority of SCD6 aggregates to multiple granules enriched at the nuclear periphery that recruit both P-body and stress granule proteins, as well as mRNAs. Granule protein composition depends on granule distance to the nucleus. In contrast to findings in yeast and humans, granule formation does not correlate with translational repression and can also take place in the nucleus after nuclear targeting of SCD6. While the SCD6 Lsm domain alone is both necessary and sufficient for granule induction, the RGG motif determines granule type and number: the absence of an intact RGG motif results in the formation of fewer granules that resemble P-bodies. The differences in granule number remain after nuclear targeting, indicating translation-independent functions of the RGG domain. We propose that, in trypanosomes, a local increase in SCD6 concentration may be sufficient to induce granules by recruiting mRNA. Proteins that bind selectively to the RGG and/or Lsm domain of SCD6 could be responsible for regulating granule type and number.

APA, Harvard, Vancouver, ISO, and other styles

2

An, Haiyan, Jing Tong Tan, and Tatyana A. Shelkovnikova. "Stress granules regulate stress-induced paraspeckle assembly." Journal of Cell Biology 218, no. 12 (October 21, 2019): 4127–40. http://dx.doi.org/10.1083/jcb.201904098.

Full text

Abstract:

Eukaryotic cells contain a variety of RNA-protein macrocomplexes termed RNP granules. Different types of granules share multiple protein components; however, the crosstalk between spatially separated granules remains unaddressed. Paraspeckles and stress granules (SGs) are prototypical RNP granules localized exclusively in the nucleus and cytoplasm, respectively. Both granules are implicated in human diseases, such as amyotrophic lateral sclerosis. We characterized the composition of affinity-purified paraspeckle-like structures and found a significant overlap between the proteomes of paraspeckles and SGs. We further show that paraspeckle hyperassembly is typical for cells subjected to SG-inducing stresses. Using chemical and genetic disruption of SGs, we demonstrate that formation of microscopically visible SGs is required to trigger and maintain stress-induced paraspeckle assembly. Mechanistically, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their inhibitory effect on paraspeckles. Our study reveals a novel function for SGs as positive regulators of nuclear RNP granule assembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease.

APA, Harvard, Vancouver, ISO, and other styles

3

Hanazawa, Momoyo, Masafumi Yonetani, and Asako Sugimoto. "PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans." Journal of Cell Biology 192, no. 6 (March 14, 2011): 929–37. http://dx.doi.org/10.1083/jcb.201010106.

Full text

Abstract:

Germ granules are germ lineage–specific ribonucleoprotein (RNP) complexes, but how they are assembled and specifically segregated to germ lineage cells remains unclear. Here, we show that the PGL proteins PGL-1 and PGL-3 serve as the scaffold for germ granule formation in Caenorhabditis elegans. Using cultured mammalian cells, we found that PGL proteins have the ability to self-associate and recruit RNPs. Depletion of PGL proteins from early C. elegans embryos caused dispersal of other germ granule components in the cytoplasm, suggesting that PGL proteins are essential for the architecture of germ granules. Using a structure–function analysis in vivo, we found that two functional domains of PGL proteins contribute to germ granule assembly: an RGG box for recruiting RNA and RNA-binding proteins and a self-association domain for formation of globular granules. We propose that self-association of scaffold proteins that can bind to RNPs is a general mechanism by which large RNP granules are formed.

APA, Harvard, Vancouver, ISO, and other styles

4

Davis, Michael, Andrea Montalbano, Megan P. Wood, and Jennifer A. Schisa. "Biphasic adaptation to osmotic stress in the C. elegans germ line." American Journal of Physiology-Cell Physiology 312, no. 6 (June 1, 2017): C741—C748. http://dx.doi.org/10.1152/ajpcell.00364.2016.

Full text

Abstract:

Cells respond to environmental stress in multiple ways. In the germ line, heat shock and nutritive stress trigger the assembly of large ribonucleoprotein (RNP) granules via liquid-liquid phase separation (LLPS). The RNP granules are hypothesized to maintain the quality of oocytes during stress. The goal of this study was to investigate the cellular response to glucose in the germ line and determine if it is an osmotic stress response. We found that exposure to 500 mM glucose induces the assembly of RNP granules in the germ line within 1 h. Interestingly, the RNP granules are maintained for up to 3 h; however, they dissociate after longer periods of stress. The RNP granules include processing body and stress granule proteins, suggesting shared functions. Based on several lines of evidence, the germ line response to glucose largely appears to be an osmotic stress response, thus identifying osmotic stress as a trigger of LLPS. Although RNP granules are not maintained beyond 3 h of osmotic stress, the quality of oocytes does not appear to decrease after longer periods of stress, suggesting a secondary adaptation in the germ line. We used an indirect marker of glycerol and observed high levels after 5 and 20 h of glucose exposure. Moreover, in gpdh-1;gpdh-2 germ lines, glycerol levels are reduced concomitant with RNP granules being maintained for an extended period. We speculate that increased glycerol levels may function as a secondary osmoregulatory adaptive response in the germ line, following a primary response of RNP granule assembly.

APA, Harvard, Vancouver, ISO, and other styles

5

Aoki, Scott T., Aaron M. Kershner, Craig A. Bingman, Marvin Wickens, and Judith Kimble. "PGL germ granule assembly protein is a base-specific, single-stranded RNase." Proceedings of the National Academy of Sciences 113, no. 5 (January 19, 2016): 1279–84. http://dx.doi.org/10.1073/pnas.1524400113.

Full text

Abstract:

Cellular RNA-protein (RNP) granules are ubiquitous and have fundamental roles in biology and RNA metabolism, but the molecular basis of their structure, assembly, and function is poorly understood. Using nematode “P-granules” as a paradigm, we focus on the PGL granule scaffold protein to gain molecular insights into RNP granule structure and assembly. We first identify a PGL dimerization domain (DD) and determine its crystal structure. PGL-1 DD has a novel 13 α-helix fold that creates a positively charged channel as a homodimer. We investigate its capacity to bind RNA and discover unexpectedly that PGL-1 DD is a guanosine-specific, single-stranded endonuclease. Discovery of the PGL homodimer, together with previous results, suggests a model in which the PGL DD dimer forms a fundamental building block for P-granule assembly. Discovery of the PGL RNase activity expands the role of RNP granule assembly proteins to include enzymatic activity in addition to their job as structural scaffolds.

APA, Harvard, Vancouver, ISO, and other styles

6

Van Treeck, Briana, David S. W. Protter, Tyler Matheny, Anthony Khong, Christopher D. Link, and Roy Parker. "RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome." Proceedings of the National Academy of Sciences 115, no. 11 (February 26, 2018): 2734–39. http://dx.doi.org/10.1073/pnas.1800038115.

Full text

Abstract:

Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited. Stress granules are thought to form by protein–protein interactions of RNA-binding proteins. We demonstrate RNA homopolymers or purified cellular RNA forms assemblies in vitro analogous to stress granules. Remarkably, under conditions representative of an intracellular stress response, the mRNAs enriched in assemblies from total yeast RNA largely recapitulate the stress granule transcriptome. We suggest stress granules are formed by a summation of protein–protein and RNA–RNA interactions, with RNA self-assembly likely to contribute to other RNP assemblies wherever there is a high local concentration of RNA. RNA assembly in vitro is also increased by GR and PR dipeptide repeats, which are known to increase stress granule formation in cells. Since GR and PR dipeptides are involved in neurodegenerative diseases, this suggests that perturbations increasing RNA–RNA assembly in cells could lead to disease.

APA, Harvard, Vancouver, ISO, and other styles

7

An, Haiyan, and Tatyana A. Shelkovnikova. "Stress granules regulate paraspeckles: RNP granule continuum at work." Cell Stress 3, no. 12 (December 9, 2019): 385–87. http://dx.doi.org/10.15698/cst2019.12.207.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Noble, Scott L., Brittany L. Allen, Lai Kuan Goh, Kristen Nordick, and Thomas C. Evans. "Maternal mRNAs are regulated by diverse P body–related mRNP granules during early Caenorhabditis elegans development." Journal of Cell Biology 182, no. 3 (August 11, 2008): 559–72. http://dx.doi.org/10.1083/jcb.200802128.

Full text

Abstract:

Processing bodies (P bodies) are conserved mRNA–protein (mRNP) granules that are thought to be cytoplasmic centers for mRNA repression and degradation. However, their specific functions in vivo remain poorly understood. We find that repressed maternal mRNAs and their regulators localize to P body–like mRNP granules in the Caenorhabditis elegans germ line. Surprisingly, several distinct types of regulated granules form during oocyte and embryo development. 3′ untranslated region elements direct mRNA targeting to one of these granule classes. The P body factor CAR-1/Rap55 promotes association of repressed mRNA with granules and contributes to repression of Notch/glp-1 mRNA. However, CAR-1 controls Notch/glp-1 only during late oogenesis, where it functions with the RNA-binding regulators PUF-5, PUF-6, and PUF-7. The P body protein CGH-1/Rck/Dhh1 differs from CAR-1 in control of granule morphology and promotes mRNP stability in arrested oocytes. Therefore, a system of diverse and regulated RNP granules elicits stage-specific functions that ensure proper mRNA control during early development.

APA, Harvard, Vancouver, ISO, and other styles

9

De Graeve, Fabienne, and Florence Besse. "Neuronal RNP granules: from physiological to pathological assemblies." Biological Chemistry 399, no. 7 (June 27, 2018): 623–35. http://dx.doi.org/10.1515/hsz-2018-0141.

Full text

Abstract:

Abstract Neuronal cells rely on macro- and micro-cellular compartmentalization to rapidly process information, and respond locally to external stimuli. Such a cellular organization is achieved via the assembly of neuronal ribonucleoprotein (RNP) granules, dynamic membrane-less organelles enriched in RNAs and associated regulatory proteins. In this review, we discuss how these high-order structures transport mRNAs to dendrites and axons, and how they contribute to the spatio-temporal regulation of localized mRNA translation. We also highlight how recent biophysical studies have shed light on the mechanisms underlying neuronal RNP granule dynamic assembly, remodeling and maturation, in both physiological and pathological contexts.

APA, Harvard, Vancouver, ISO, and other styles

10

Corbet, Giulia Ada, and Roy Parker. "RNP Granule Formation: Lessons from P-Bodies and Stress Granules." Cold Spring Harbor Symposia on Quantitative Biology 84 (2019): 203–15. http://dx.doi.org/10.1101/sqb.2019.84.040329.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Burke, James M., Evan T. Lester, Devin Tauber, and Roy Parker. "RNase L promotes the formation of unique ribonucleoprotein granules distinct from stress granules." Journal of Biological Chemistry 295, no. 6 (January 2, 2020): 1426–38. http://dx.doi.org/10.1074/jbc.ra119.011638.

Full text

Abstract:

Stress granules (SGs) are ribonucleoprotein (RNP) assemblies that form in eukaryotic cells as a result of limited translation in response to stress. SGs form during viral infection and are thought to promote the antiviral response because many viruses encode inhibitors of SG assembly. However, the antiviral endoribonuclease RNase L also alters SG formation, whereby only small punctate SG-like bodies that we term RNase L–dependent bodies (RLBs) form during RNase L activation. How RLBs relate to SGs and their mode of biogenesis is unknown. Herein, using immunofluorescence, live-cell imaging, and MS-based analyses, we demonstrate that RLBs represent a unique RNP granule with a protein and RNA composition distinct from that of SGs in response to dsRNA lipofection in human cells. We found that RLBs are also generated independently of SGs and the canonical dsRNA-induced SG biogenesis pathway, because RLBs did not require protein kinase R, phosphorylation of eukaryotic translation initiation factor 2 subunit 1 (eIF2α), the SG assembly G3BP paralogs, or release of mRNAs from ribosomes via translation elongation. Unlike the transient interactions between SGs and P-bodies, RLBs and P-bodies extensively and stably interacted. However, despite both RLBs and P-bodies exhibiting liquid-like properties, they remained distinct condensates. Taken together, these observations reveal that RNase L promotes the formation of a unique RNP complex that may have roles during the RNase L–mediated antiviral response.

APA, Harvard, Vancouver, ISO, and other styles

12

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

13

Hubstenberger, Arnaud, Cristiana Cameron, Scott L. Noble, Sean Keenan, and Thomas C. Evans. "Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development." Journal of Cell Biology 211, no. 3 (November 2, 2015): 703–16. http://dx.doi.org/10.1083/jcb.201504044.

Full text

Abstract:

Ribonucleoproteins (RNPs) often coassemble into supramolecular bodies with regulated dynamics. The factors controlling RNP bodies and connections to RNA regulation are unclear. During Caenorhabditis elegans oogenesis, cytoplasmic RNPs can transition among diffuse, liquid, and solid states linked to mRNA regulation. Loss of CGH-1/Ddx6 RNA helicase generates solid granules that are sensitive to mRNA regulators. Here, we identified 66 modifiers of RNP solids induced by cgh-1 mutation. A majority of genes promote or suppress normal RNP body assembly, dynamics, or metabolism. Surprisingly, polyadenylation factors promote RNP coassembly in vivo, suggesting new functions of poly(A) tail regulation in RNP dynamics. Many genes carry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating possible connections with neurodegenerative disorders induced by CAG/polyQ expansion. Several RNP body regulators repress translation of mRNA subsets, suggesting that mRNAs are repressed by multiple mechanisms. Collectively, these findings suggest new pathways of RNP modification that control large-scale coassembly and mRNA activity during development.

APA, Harvard, Vancouver, ISO, and other styles

14

Rhine, Kevin, Velinda Vidaurre, and Sua Myong. "RNA Droplets." Annual Review of Biophysics 49, no. 1 (May 6, 2020): 247–65. http://dx.doi.org/10.1146/annurev-biophys-052118-115508.

Full text

Abstract:

Liquid–liquid phase separation is emerging as the universal mechanism by which membraneless cellular granules form. Despite many previous studies on condensation of intrinsically disordered proteins and low complexity domains, we lack understanding about the role of RNA, which is the essential component of all ribonucleoprotein (RNP) granules. RNA, as an anionic polymer, is inherently an excellent platform for achieving multivalency and can accommodate many RNA binding proteins. Recent findings have highlighted the diverse function of RNA in tuning phase-separation propensity up or down, altering viscoelastic properties and thereby driving immiscibility between different condensates. In addition to contributing to the biophysical properties of droplets, RNA is a functionally critical constituent that defines the identity of cellular condensates and controls the temporal and spatial distribution of specific RNP granules. In this review, we summarize what we have learned so far about such roles of RNA in the context of in vitro and in vivo studies.

APA, Harvard, Vancouver, ISO, and other styles

15

Short, Ben. "Solidifying the view of RNP dynamics." Journal of Cell Biology 211, no. 3 (November 2, 2015): 487. http://dx.doi.org/10.1083/jcb.2113if.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Lehtiniemi, Tiina, and Noora Kotaja. "Germ granule-mediated RNA regulation in male germ cells." Reproduction 155, no. 2 (February 2018): R77—R91. http://dx.doi.org/10.1530/rep-17-0356.

Full text

Abstract:

Germ cells have exceptionally diverse transcriptomes. Furthermore, the progress of spermatogenesis is accompanied by dramatic changes in gene expression patterns, the most drastic of them being near-to-complete transcriptional silencing during the final steps of differentiation. Therefore, accurate RNA regulatory mechanisms are critical for normal spermatogenesis. Cytoplasmic germ cell-specific ribonucleoprotein (RNP) granules, known as germ granules, participate in posttranscriptional regulation in developing male germ cells. Particularly, germ granules provide platforms for the PIWI-interacting RNA (piRNA) pathway and appear to be involved both in piRNA biogenesis and piRNA-targeted RNA degradation. Recently, other RNA regulatory mechanisms, such as the nonsense-mediated mRNA decay pathway have also been associated to germ granules providing new exciting insights into the function of germ granules. In this review article, we will summarize our current knowledge on the role of germ granules in the control of mammalian male germ cell’s transcriptome and in the maintenance of fertility.

APA, Harvard, Vancouver, ISO, and other styles

17

Rao, Bhalchandra S., and Roy Parker. "Numerous interactions act redundantly to assemble a tunable size of P bodies in Saccharomyces cerevisiae." Proceedings of the National Academy of Sciences 114, no. 45 (October 23, 2017): E9569—E9578. http://dx.doi.org/10.1073/pnas.1712396114.

Full text

Abstract:

Eukaryotic cells contain multiple RNA–protein assemblies referred to as RNP granules, which are thought to form through multiple protein–protein interactions analogous to a liquid–liquid phase separation. One class of RNP granules consists of P bodies, which consist of nontranslating mRNAs and the general translation repression and mRNA degradation machinery. P bodies have been suggested to form predominantly through interactions of Edc3 and a prion-like domain on Lsm4. In this work, we provide evidence that P-body assembly can be driven by multiple different protein–protein and/or protein–RNA interactions, including interactions involving Dhh1, Psp2, and Pby1. Moreover, the relative importance of specific interactions can vary with different growth conditions. Based on these observations, we develop a summative model wherein the P-body assembly phenotype of a given mutant can be predicted from the number of currently known protein–protein interactions between P-body components.

APA, Harvard, Vancouver, ISO, and other styles

18

ABOLHASSANI-DADRAS, S., G. H. VÁZQUEZ-NIN, O. M. ECHEVERRÍA, V. BOUTINARD ROUELLE-ROSSIER, and S. FAKAN. "ESI in situ analyses of extrachromosomal RNP granules." Journal of Microscopy 174, no. 3 (June 1994): 233–38. http://dx.doi.org/10.1111/j.1365-2818.1994.tb03470.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Glätzer, K. H., and P. M. Kloetzel. "Differential chromosomal distribution of ribonucleoprotein antigens in nuclei of Drosophila spermatocytes." Journal of Cell Biology 103, no. 6 (December 1, 1986): 2113–19. http://dx.doi.org/10.1083/jcb.103.6.2113.

Full text

Abstract:

The ribonucleoprotein (RNP) composition of the active Y chromosomal structures in spermatocyte nuclei of Drosophila hydei has been investigated using the anti-RNP antibodies Dm 28K2 and pp60 as a probe. Antibody Dm 28K2 was raised against an RNP protein of cytoplasmic RNP particles in D. melanogaster cells, while antibody pp60 was raised against a pre-messenger RNP fraction from oocytes of Xenopus laevis. Both antibodies detect nuclear RNP (nRNP) antigens of D. hydei. This is shown by CsCl density centrifugation of nRNP from D. hydei cells and immunoblotting across the density gradient. Dm 28K2 and pp60 recognize antigens of nRNP complexes which band at a characteristic buoyant density of approximately 1.4 g/cm3 in CsCl. By indirect immunofluorescence we observe that the nRNP complexes identified by Dm 28K2 are localized at only two of the five Y chromosomal loop structures which are named according to their distinct morphology. Dm 28K2 decorates RNPs within the "clubs," within the cones, and within the matrix of the "pseudonucleolus." Ultrastructural bodies that are candidates for this immunoreaction are RNP granules that resemble the so-called perichromatin granules. Antibody pp60 recognizes RNP complexes close to the axes of the active Y chromatin. In the "pseudonucleolus" it can be shown that the structures recognized by pp60 are quite distinct from those detected by Dm 28K2. Thus, the "pseudonucleolus" is a striking example for the presence of different RNP populations within a same defined nuclear compartment. Together with previous results (Glätzer, K. H., 1984, Mol. Gen. Genet., 196:236-243), our data represent evidence that the morphological and apparently functional differences between the active Y chromosomal loops, which are involved in male fertility, are caused by the presence of qualitatively and possibly also functionally different RNP populations within these nuclear compartments. Because both RNP antigens are discussed in the literature in connection with repressed mRNP the observed cross-reaction of the respective antibodies in D. hydei suggests a more general and important function of these proteins in the RNA metabolism of eukaryotic cells.

APA, Harvard, Vancouver, ISO, and other styles

20

Abolhassani-Dadras, S., G. H. Vázquez-Nin, O. M. Echeverría, and S. Fakan. "The use of an internal standard in the application of quantitative image-EELS in biology." Proceedings, annual meeting, Electron Microscopy Society of America 54 (August 11, 1996): 50–51. http://dx.doi.org/10.1017/s0424820100162715.

Full text

Abstract:

The energy filtering transmission electron microscope (EFTEM) is employed to examine the possibility of using ribosomes as internal standard for a quantitative in-situ study of phosphorus content of nuclear constituents in a biological section. The problems that can arise from different steps of such an experimental approach are discussed.Salivary gland cells from fourth instar larvae of Chironomus thummi are selected as test specimens because of their appropriate structure. The nucleus of these cells contains two types of granules, one of which (known as Balbiani ring granule, Brg) has an RNA size known from radioactive phosphorus labelling and subsequent isolation, allowing one to estimate its phosphorus content. The other type of granule (known as small RNP granule) has been recently discovered and its phosphorus content is not known. The EFTEM method is used to verify the phosphorus content of these two nuclear constituents.

APA, Harvard, Vancouver, ISO, and other styles

21

Biggiogera, Marco, Maria Grazia Bottone, and Carlo Pellicciari. "Nuclear RNA Is Extruded from Apoptotic Cells." Journal of Histochemistry & Cytochemistry 46, no. 9 (September 1998): 999–1005. http://dx.doi.org/10.1177/002215549804600903.

Full text

Abstract:

During spontaneous apoptosis of thymocytes there is extrusion of ribonucleoproteins (RNPs) from the cell. The aim of this investigation was to elucidate whether the RNP aggregates in apoptotic cells and bodies still contain RNA in an appreciable amount. We demonstrated by specific cytochemical techniques that the aggregates of nuclear RNPs extruded in the cytoplasm of spontaneously apoptotic thymocytes contain RNA in a sufficient amount to be detected cytochemically. These heterogeneous ectopic RNP-derived structures (HERDS) are formed by perichromatin fibrils, interchromatin granules, perichromatin granules, and nucleolar material. The RNA detected inside these clusters should therefore correspond to both mRNA and snRNA as well as to rRNA. We never observed DNA-contaning aggregates in the cytoplasm of apoptotic thymocytes. The presence of RNA in the HERDS that may be released from apoptotic cells suggests that the decrease in the amount of total RNA during apoptosis may be mostly linked to cellular extrusion rather than to degradation of RNA by RNase activities. Another interesting aspect of these results lies in the hypothesis of apoptosis as a possible cause for the presence of autoantibodies in the serum of patients with systemic autoimmune diseases.

APA, Harvard, Vancouver, ISO, and other styles

22

Goodier, John L., Lili Zhang, Melissa R. Vetter, and Haig H. Kazazian. "LINE-1 ORF1 Protein Localizes in Stress Granules with Other RNA-Binding Proteins, Including Components of RNA Interference RNA-Induced Silencing Complex." Molecular and Cellular Biology 27, no. 18 (June 11, 2007): 6469–83. http://dx.doi.org/10.1128/mcb.00332-07.

Full text

Abstract:

ABSTRACT LINE-1 retrotransposons constitute one-fifth of human DNA and have helped shape our genome. A full-length L1 encodes a 40-kDa RNA-binding protein (ORF1p) and a 150-kDa protein (ORF2p) with endonuclease and reverse transcriptase activities. ORF1p is distinctive in forming large cytoplasmic foci, which we identified as cytoplasmic stress granules. A phylogenetically conserved central region of the protein is critical for wild-type localization and retrotransposition. Yeast two-hybrid screens revealed several RNA-binding proteins that coimmunoprecipitate with ORF1p and colocalize with ORF1p in foci. Two of these proteins, YB-1 and hnRNPA1, were previously reported in stress granules. We identified additional proteins associated with stress granules, including DNA-binding protein A, 9G8, and plasminogen activator inhibitor RNA-binding protein 1 (PAI-RBP1). PAI-RBP1 is a homolog of VIG, a part of the Drosophila melanogaster RNA-induced silencing complex (RISC). Other RISC components, including Ago2 and FMRP, also colocalize with PAI-RBP1 and ORF1p. We suggest that targeting ORF1p, and possibly the L1 RNP, to stress granules is a mechanism for controlling retrotransposition and its associated genetic and cellular damage.

APA, Harvard, Vancouver, ISO, and other styles

23

Standart, Nancy, and Nicola Minshall. "Translational control in early development: CPEB, P-bodies and germinal granules." Biochemical Society Transactions 36, no. 4 (July 22, 2008): 671–76. http://dx.doi.org/10.1042/bst0360671.

Full text

Abstract:

Selective protein synthesis in oocytes, eggs and early embryos of many organisms drives several critical aspects of early development, including meiotic maturation and entry into mitosis, establishment of embryonic axes and cell fate determination. mRNA-binding proteins which (usually) recognize 3′-UTR (untranslated region) elements in target mRNAs influence the recruitment of the small ribosomal subunit to the 5′ cap. Probably the best studied such protein is CPEB (cytoplasmic polyadenylation element-binding protein), which represses translation in the oocyte in a cap-dependent manner, and activates translation in the meiotically maturing egg, via cytoplasmic polyadenylation. Co-immunoprecipitation and gel-filtration assays revealed that CPEB in Xenopus oocytes is in a very large RNP (ribonucleoprotein) complex and interacts with other RNA-binding proteins including Xp54 RNA helicase, Pat1, RAP55 (RNA-associated protein 55) and FRGY2 (frog germ cell-specific Y-box protein 2), as well as the eIF4E (eukaryotic initiation factor 4E)-binding protein 4E-T (eIF4E-transporter) and an ovary-specific eIF4E1b, which binds the cap weakly. Functional tests which implicate 4E-T and eIF4E1b in translational repression in oocytes led us to propose a model for the specific inhibition of translation of a target mRNA by a weak cap-binding protein. The components of the CPEB RNP complex are common to P-bodies (processing bodies), neuronal granules and germinal granules, suggesting that a highly conserved ‘masking’ complex operates in early development, neurons and somatic cells.

APA, Harvard, Vancouver, ISO, and other styles

24

Zhang, Yi, Jiayu Gu, and Qiming Sun. "Aberrant Stress Granule Dynamics and Aggrephagy in ALS Pathogenesis." Cells 10, no. 9 (August 30, 2021): 2247. http://dx.doi.org/10.3390/cells10092247.

Full text

Abstract:

Stress granules are conserved cytosolic ribonucleoprotein (RNP) compartments that undergo dynamic assembly and disassembly by phase separation in response to stressful conditions. Gene mutations may lead to aberrant phase separation of stress granules eliciting irreversible protein aggregations. A selective autophagy pathway called aggrephagy may partially alleviate the cytotoxicity mediated by these protein aggregates. Cells must perceive when and where the stress granules are transformed into toxic protein aggregates to initiate autophagosomal engulfment for subsequent autolysosomal degradation, therefore, maintaining cellular homeostasis. Indeed, defective aggrephagy has been causally linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this review, we discuss stress granules at the intersection of autophagy and ALS pathogenesis.

APA, Harvard, Vancouver, ISO, and other styles

25

Nielsen, Finn C., Jacob Nielsen, Mette A. Kristensen, Grete Koch, and Jan Christiansen. "Cytoplasmic trafficking of IGF-II mRNA-binding protein by conserved KH domains." Journal of Cell Science 115, no. 10 (May 15, 2002): 2087–97. http://dx.doi.org/10.1242/jcs.115.10.2087.

Full text

Abstract:

The IGF-II mRNA-binding proteins (IMPs), which are composed of two RNA recognition motifs, (RRM) and four hnRNP K homology (KH) domains, have been implicated in subcytoplasmic localization of mRNAs during embryogenesis. The IMP family originated via two gene duplications before the divergence of vertebrates, and IMP homologues consisting of only the four KH motifs have been identified in Drosophila and Caenorhabditis elegans. Here we characterise the trafficking of GFP-IMP1 fusion proteins and determine the structural determinants for proper cytoplasmic localization. GFP-IMP1 is present in large 200-700 nm RNP granules, which are distributed along microtubules. In motile cells, GFP-IMP1 is transported towards the leading edge into the cortical region of the lamellipodia where it is connected to microfilaments. Granules travel in an ATP-dependent fashion at an average speed of 0.12 μm/s (range 0.04-0.22 μm/s), and cells switch from a delocalized to a localized pattern within 15-20 minutes. Both granule formation and localization are unaffected by removal of the two RRMs, whereas deletion of the KH domains, which mediate RNA-binding, impairs these functions. We conclude that IMP1 localization is associated with motility and that the major functions of IMP1 are carried out by the phylogenetically conserved KH domains.

APA, Harvard, Vancouver, ISO, and other styles

26

Desai, Perlina, and Rina Bandopadhyay. "Pathophysiological implications of RNP granules in frontotemporal dementia and ALS." Neurochemistry International 140 (November 2020): 104819. http://dx.doi.org/10.1016/j.neuint.2020.104819.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Moon, Stephanie L., Tatsuya Morisaki, Anthony Khong, Kenneth Lyon, Roy Parker, and Timothy J. Stasevich. "Multicolour single-molecule tracking of mRNA interactions with RNP granules." Nature Cell Biology 21, no. 2 (January 21, 2019): 162–68. http://dx.doi.org/10.1038/s41556-018-0263-4.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Wurtz-T, E. Kiseleva, G. Nacheva, A. Alzhanova-Ericcson, A. Rosén, and B. Daneholt. "Identification of two RNA-binding proteins in Balbiani ring premessenger ribonucleoprotein granules and presence of these proteins in specific subsets of heterogeneous nuclear ribonucleoprotein particles." Molecular and Cellular Biology 16, no. 4 (April 1996): 1425–35. http://dx.doi.org/10.1128/mcb.16.4.1425.

Full text

Abstract:

Balbiani ring (BR) granules are premessenger ribonucleoprotein particles (RNPs) generated in giant chromosomal puffs, the BRs, in the larval salivary glands of the dipteran chironomus tentans. Monoclonal antibodies were raised against nuclear proteins collected on a single-stranded-DNA-agarose affinity column, and two of them were used to identify RNA-binding proteins in BR granules. First, in Western blots (immunoblots), one of the antibodies recognized a 36-kDa protein and the other recognized a 45-KDa protein. Second, both antibodies bound to the BRs in immunocytological experiments. It was shown in cross-linking experiments that the two proteins are associated with heterogeneous nuclear RNP (hnRNP) complexes extracted from C. tentans nuclei. By immunoelectron microscopy of isolated and partly unfolded BR RNPs, it was specifically demonstrated that the BR granules contain the two proteins and, in addition, that both proteins are distributed frequently along the RNP fiber of the particles. Thus, the 36- and 45-KDa proteins are likely to be abundant, RNA-binding proteins in the BR particles. To elucidate to what extent the two proteins are also present in other hnRNPs, we studied the binding of the antibodies to chromosomal puffs in general. It was observed that many puffs in addition to the BRs harbor the two proteins, but there are also puffs containing only one of the components, either the 36- or the 45-kDa protein. We conclude that the two proteins are not randomly bound to all hnRNPs but that each of them seems to be linked to a specific subset of the particles.

APA, Harvard, Vancouver, ISO, and other styles

29

Cambray, Serafí, Neus Pedraza, Marta Rafel, Eloi Garí, Martí Aldea, and Carme Gallego. "Protein Kinase KIS Localizes to RNA Granules and Enhances Local Translation." Molecular and Cellular Biology 29, no. 3 (November 17, 2008): 726–35. http://dx.doi.org/10.1128/mcb.01180-08.

Full text

Abstract:

ABSTRACT The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the β-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3′ untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.

APA, Harvard, Vancouver, ISO, and other styles

30

Pizzinga, Mariavittoria, Christian Bates, Jennifer Lui, Gabriella Forte, Fabián Morales-Polanco, Emma Linney, Barbora Knotkova, et al. "Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth." Journal of Cell Biology 218, no. 5 (March 15, 2019): 1564–81. http://dx.doi.org/10.1083/jcb.201704019.

Full text

Abstract:

mRNA localization serves key functions in localized protein production, making it critical that the translation machinery itself is present at these locations. Here we show that translation factor mRNAs are localized to distinct granules within yeast cells. In contrast to many messenger RNP granules, such as processing bodies and stress granules, which contain translationally repressed mRNAs, these granules harbor translated mRNAs under active growth conditions. The granules require Pab1p for their integrity and are inherited by developing daughter cells in a She2p/She3p-dependent manner. These results point to a model where roughly half the mRNA for certain translation factors is specifically directed in granules or translation factories toward the tip of the developing daughter cell, where protein synthesis is most heavily required, which has particular implications for filamentous forms of growth. Such a feedforward mechanism would ensure adequate provision of the translation machinery where it is to be needed most over the coming growth cycle.

APA, Harvard, Vancouver, ISO, and other styles

31

Semeshin, V. F., I. F. Zhimulev, D. Kritikou, and A. Zacharopoulou. "Electron microscope investigation of polytene chromosomes in the Mediterranean fruit fly Ceratitis capitata." Genome 38, no. 4 (August 1, 1995): 652–60. http://dx.doi.org/10.1139/g95-083.

Full text

Abstract:

Ultrastructural analyses of polytene chromosomes from male pupal orbital bristle cells and from larval salivary glands of Ceratitis capitata were carried out. It was shown that chromatin complexes corresponding to the X chromosome heterochromatic network are surrounded by material containing ribonucleoprotein (RNP) granules 250–300 Å (1 Å = 0.1 nm) in diameter. RNP granules of similar size surround the spherical Y chromosome. These data point out the presence of transcriptional activity in both of these chromosomes. The absence of clear structure in chromosomal regions situated between large bands in both types of tissues was observed. These results support the hypothesis of weak synapsis between chromatids or small chromomeres of polytene chromosomes in this species. In addition, we describe a specific puff revealed in both orbital trichogen cells and salivary glands that is morphologically similar to the 93D puff of Drosophila melanogaster.Key words: Ceratitis capitata, polytene chromosomes, electron microscopy.

APA, Harvard, Vancouver, ISO, and other styles

32

Kaur, Taranpreet, Ibraheem Alshareedah, Wei Wang, Jason Ngo, Mahdi Moosa, and Priya Banerjee. "Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates." Biomolecules 9, no. 2 (February 19, 2019): 71. http://dx.doi.org/10.3390/biom9020071.

Full text

Abstract:

Ribonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to a changing cellular environment. RNP condensation is largely governed by promiscuous attractive inter-chain interactions mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, fused in sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid–liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with an excluded volume model. With increasing bulk crowder concentration, the RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to viscoelastic gel-like states in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent commonly occurring sequence motifs driving RNP phase transitions, we reveal that the impact of crowding is largely independent of LCD charge and sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction, which suggests that inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play a key role in tuning the physical properties of RNP condensates within the crowded cellular space.

APA, Harvard, Vancouver, ISO, and other styles

33

Olins, Ada L., Donald E. Olins, Manesh B. Shah, Henri A. Levy, and David P. Bazett-Jonest. "The 3-D substructure of RNA in nascent RNP granules: A novel application of osmium ammine-B staining and electron spectroscopic imaging." Proceedings, annual meeting, Electron Microscopy Society of America 50, no. 1 (August 1992): 504–5. http://dx.doi.org/10.1017/s0424820100122927.

Full text

Abstract:

RNA has a particulate substructure when visualized in situ with the nucleic acid specific stain osmium ammine-B (OA-B). In this study energy spectroscopic imaging (ESI) was used to enhance the contrast and collect the data for tomographic reconstructions.The Balbiani ring (BR) in the salivary gland polytene chromosomes of Chironomus tentans larvae furnishes a well known model for the structure of nascent m-RNA. This gland produces copious amounts of silk-like secretory proteins which are very large (106 daltons). The site of transcription, the BR, is easily recognized in the EM by its characteristic “puff” structure and electron-dense granular transcripts. Mature BR granules are 45-50 nm in diameter and can be easily observed within the nucleus and passing through nuclear pores.

APA, Harvard, Vancouver, ISO, and other styles

34

Iwaki, Aya, Takao Kawai, Yosuke Yamamoto, and Shingo Izawa. "Biomass Conversion Inhibitors Furfural and 5-Hydroxymethylfurfural Induce Formation of Messenger RNP Granules and Attenuate Translation Activity in Saccharomyces cerevisiae." Applied and Environmental Microbiology 79, no. 5 (December 28, 2012): 1661–67. http://dx.doi.org/10.1128/aem.02797-12.

Full text

Abstract:

ABSTRACTVarious forms of stress can cause an attenuation of bulk translation activity and the accumulation of nontranslating mRNAs into cytoplasmic messenger RNP (mRNP) granules termed processing bodies (P-bodies) and stress granules (SGs) in eukaryotic cells. Furfural and 5-hydroxymethylfurfural (HMF), derived from lignocellulosic biomass, inhibit yeast growth and fermentation as stressors. Since there is no report regarding their effects on the formation of cytoplasmic mRNP granules, here we investigated whether furfural and HMF cause the assembly of yeast P-bodies and SGs accompanied by translational repression. We found that furfural and HMF cause the attenuation of bulk translation activity and the assembly of cytoplasmic mRNP granules inSaccharomyces cerevisiae. Notably, a combination of furfural and HMF induced the remarkable repression of translation initiation and SG formation. These findings provide new information about the physiological effects of furfural and HMF on yeast cells, and also suggest the potential usefulness of cytoplasmic mRNP granules as a warning sign or index of the deterioration of cellular physiological status in the fermentation of lignocellulosic hydrolysates.

APA, Harvard, Vancouver, ISO, and other styles

35

Soop, Teresa, Birgitta Ivarsson, Birgitta Björkroth, Nathalie Fomproix, Sergej Masich, Volker C. Cordes, and Bertil Daneholt. "Nup153 Affects Entry of Messenger and Ribosomal Ribonucleoproteins into the Nuclear Basket during Export." Molecular Biology of the Cell 16, no. 12 (December 2005): 5610–20. http://dx.doi.org/10.1091/mbc.e05-08-0715.

Full text

Abstract:

A specific messenger ribonucleoprotein (RNP) particle, Balbiani ring (BR) granules in the dipteran Chironomus tentans, can be visualized during passage through the nuclear pore complex (NPC). We have now examined the transport through the nuclear basket preceding the actual translocation through the NPC. The basket consists of eight fibrils anchored to the NPC core by nucleoprotein Nup153. On nuclear injection of anti-Nup153, the transport of BR granules is blocked. Many granules are retained on top of the nuclear basket, whereas no granules are seen in transit through NPC. Interestingly, the effect of Nup153 seems distant from the antibody-binding site at the base of the basket. We conclude that the entry into the basket is a two-step process: an mRMP first binds to the tip of the basket fibrils and only then is it transferred into the basket by a Nup153-dependent process. It is indicated that ribosomal subunits follow a similar pathway.

APA, Harvard, Vancouver, ISO, and other styles

36

Naarmann, I. S., C. Harnisch, G. Muller-Newen, H. Urlaub, A. Ostareck-Lederer, and D. H. Ostareck. "DDX6 recruits translational silenced human reticulocyte 15-lipoxygenase mRNA to RNP granules." RNA 16, no. 11 (September 30, 2010): 2189–204. http://dx.doi.org/10.1261/rna.2211110.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Krüger, Tim, Hanswalter Zentgraf, and Ulrich Scheer. "Intranucleolar sites of ribosome biogenesis defined by the localization of early binding ribosomal proteins." Journal of Cell Biology 177, no. 4 (May 21, 2007): 573–78. http://dx.doi.org/10.1083/jcb.200612048.

Full text

Abstract:

Considerable efforts are being undertaken to elucidate the processes of ribosome biogenesis. Although various preribosomal RNP complexes have been isolated and molecularly characterized, the order of ribosomal protein (r-protein) addition to the emerging ribosome subunits is largely unknown. Furthermore, the correlation between the ribosome assembly pathway and the structural organization of the dedicated ribosome factory, the nucleolus, is not well established. We have analyzed the nucleolar localization of several early binding r-proteins in human cells, applying various methods, including live-cell imaging and electron microscopy. We have located all examined r-proteins (S4, S6, S7, S9, S14, and L4) in the granular component (GC), which is the nucleolar region where later pre-ribosomal RNA (rRNA) processing steps take place. These results imply that early binding r-proteins do not assemble with nascent pre-rRNA transcripts in the dense fibrillar component (DFC), as is generally believed, and provide a link between r-protein assembly and the emergence of distinct granules at the DFC–GC interface.

APA, Harvard, Vancouver, ISO, and other styles

38

Aronov, Stella, Saray Dover-Biterman, Edith Suss-Toby, Michael Shmoish, Lea Duek, and Mordechai Choder. "Pheromone-encoding mRNA is transported to the yeast mating projection by specific RNP granules." Journal of Cell Biology 209, no. 6 (June 22, 2015): 829–42. http://dx.doi.org/10.1083/jcb.201408045.

Full text

Abstract:

Association of messenger RNAs with large complexes such as processing bodies (PBs) plays a pivotal role in regulating their translation and decay. Little is known about other possible functions of these assemblies. Exposure of haploid yeast cells, carrying mating type “a,” to “α pheromone” stimulates polarized growth resulting in a “shmoo” projection; it also induces synthesis of “a pheromone,” encoded by MFA2. In this paper, we show that, in response to α pheromone, MFA2 mRNA is assembled with two types of granules; both contain some canonical PB proteins, yet they differ in size, localization, motility, and sensitivity to cycloheximide. Remarkably, one type is involved in mRNA transport to the tip of the shmoo, whereas the other—in local translation in the shmoo. Normal assembly of these granules is critical for their movement, localization, and for mating. Thus, MFA2 mRNAs are transported to the shmoo tip, in complex with PB-like particles, where they are locally translated.

APA, Harvard, Vancouver, ISO, and other styles

39

Kato, Yasuko, and Akira Nakamura. "Roles of cytoplasmic RNP granules in intracellular RNA localization and translational control in the Drosophila oocyte." Development, Growth & Differentiation 54, no. 1 (November 24, 2011): 19–31. http://dx.doi.org/10.1111/j.1440-169x.2011.01314.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Bhatter, Nupur, Rajan Iyyappan, Gayatri Mohanan, and Purusharth I. Rajyaguru. "Exploring the role of RRM domains and conserved aromatic residues in RGG motif of eIF4G-binding translation repressor protein Sbp1." Wellcome Open Research 3 (September 17, 2021): 102. http://dx.doi.org/10.12688/wellcomeopenres.14709.3.

Full text

Abstract:

Background: RNA binding proteins play crucial role in determining if a given mRNA will be translated, stored, or degraded. Sbp1 is an RGG-motif containing protein that is implicated in affecting mRNA decapping and translation. Sbp1 represses translation by binding eIF4G1 through its RGG-motif and activates decapping when overexpressed. In this report, we have assessed the genetic interaction of Sbp1 with decapping activators such as Dhh1, Pat1, and Scd6. We have further analyzed the importance of different domains and specific conserved residues of Sbp1 in its ability to cause over-expression mediated growth defect. Method: Sequence alignment was performed to identify conserved aromatic residues to be mutated. Using site-directed mutagenesis several point mutations and domain deletions were created in Sbp1 expressed under a galactose-inducible promoter. The mutants were tested for their ability to cause growth defect upon over-expression. The ability of Sbp1 to affect over-expression mediated growth defect of other decapping activators was tested using growth assay. Live cell imaging was done to study localization of Sbp1 and its RRM-deletion mutants to RNA granules upon glucose starvation. Results: Mutation of several aromatic residues in the RGG-motif and that of the phosphorylation sites in the RRM domain of Sbp1 did not affect the growth defect phenotype. Deletion of another eIF4G1-binding RGG-motif protein Scd6 does not affect the ability of Sbp1 to cause growth defect. Moreover, absence of Sbp1 did not affect the growth defect phenotypes observed upon overexpression of decapping activators Dhh1 and Pat1. Strikingly deletion of both the RRM domains (RRM1 and RRM2) and not the RNP motifs within them compromised the growth defect phenotype. Sbp1 mutant lacking both RRM1 and RRM2 was highly defective in localizing to RNA granules. Conclusion: This study identifies an important role of RRM domains independent of the RNP motif in Sbp1 function.

APA, Harvard, Vancouver, ISO, and other styles

41

ABOLHAS SANI-DADRAS, S., G. H. VÁZQUEZ-NIN, O. M. ECHEVERRÍA, and S. FAKAN. "Image-EELS for in situ estimation of the phosphorus content of RNP granules." Journal of Microscopy 183, no. 3 (September 1996): 215–22. http://dx.doi.org/10.1046/j.1365-2818.1996.950653.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Ling, Shuo-Chien. "Synaptic Paths to Neurodegeneration: The Emerging Role of TDP-43 and FUS in Synaptic Functions." Neural Plasticity 2018 (2018): 1–13. http://dx.doi.org/10.1155/2018/8413496.

Full text

Abstract:

TAR DNA-binding protein-43 KDa (TDP-43) and fused in sarcoma (FUS) as the defining pathological hallmarks for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coupled with ALS-FTD-causing mutations in both genes, indicate that their dysfunctions damage the motor system and cognition. On the molecular level, TDP-43 and FUS participate in the biogenesis and metabolism of coding and noncoding RNAs as well as in the transport and translation of mRNAs as part of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules. Intriguingly, many of the RNA targets of TDP-43 and FUS are involved in synaptic transmission and plasticity, indicating that synaptic dysfunction could be an early event contributing to motor and cognitive deficits in ALS and FTD. Furthermore, the ability of the low-complexity prion-like domains of TDP-43 and FUS to form liquid droplets suggests a potential mechanism for mRNP assembly and conversion. This review will discuss the role of TDP-43 and FUS in RNA metabolism, with an emphasis on the involvement of this process in synaptic function and neuroprotection. This will be followed by a discussion of the potential phase separation mechanism for forming RNP granules and pathological inclusions.

APA, Harvard, Vancouver, ISO, and other styles

43

Ravanidis, Stylianos, Fedon-Giasin Kattan, and Epaminondas Doxakis. "Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors." International Journal of Molecular Sciences 19, no. 8 (August 3, 2018): 2280. http://dx.doi.org/10.3390/ijms19082280.

Full text

Abstract:

The timing, dosage and location of gene expression are fundamental determinants of brain architectural complexity. In neurons, this is, primarily, achieved by specific sets of trans-acting RNA-binding proteins (RBPs) and their associated factors that bind to specific cis elements throughout the RNA sequence to regulate splicing, polyadenylation, stability, transport and localized translation at both axons and dendrites. Not surprisingly, misregulation of RBP expression or disruption of its function due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to the pathogenesis of several neuropsychiatric and neurodegenerative disorders such as fragile-X syndrome, autism spectrum disorders, spinal muscular atrophy, amyotrophic lateral sclerosis and frontotemporal dementia. This review discusses the roles of Pumilio, Staufen, IGF2BP, FMRP, Sam68, CPEB, NOVA, ELAVL, SMN, TDP43, FUS, TAF15, and TIA1/TIAR in RNA metabolism by analyzing their specific molecular and cellular function, the neurological symptoms associated with their perturbation, and their axodendritic transport/localization along with their target mRNAs as part of larger macromolecular complexes termed ribonucleoprotein (RNP) granules.

APA, Harvard, Vancouver, ISO, and other styles

44

Bhatter, Nupur, Rajan Iyyappan, and Purusharth I. Rajyaguru. "Exploring the role of RRM domains and conserved aromatic residues in RGG motif of eIF4G-binding translation repressor protein Sbp1." Wellcome Open Research 3 (February 6, 2020): 102. http://dx.doi.org/10.12688/wellcomeopenres.14709.2.

Full text

Abstract:

Background: Mechanisms of mRNA fate decisions play an important role in determining if a given mRNA will be translated, stored or degraded upon arrival to cytoplasm. Sbp1 is an important RGG-motif containing protein that is implicated in affecting mRNA decapping and translation. Sbp1 represses translation by binding eIF4G1 through its RGG-motif and activates decapping when overexpressed. In this report we have assessed the genetic interaction of Sbp1 with decapping activators such as Dhh1, Pat1 and Scd6. We have further analyzed the importance of different domains and specific conserved residues of Sbp1 in translation repression activity. Method: Sequence alignment was performed to identify conserved aromatic residues to be mutated. Using site-directed mutagenesis several point mutations and domain deletions was created in Sbp1 expressed under a galactose-inducible promoter. The mutants were tested for their ability to cause growth defect upon over-expression. The ability of Sbp1 to affect over expression mediated growth defect of other decapping activators was tested using growth assay. Live cell imaging was done to study localization of Sbp1 and its RRM-deletion mutants to RNA granules upon glucose starvation. Results: Mutation of several aromatic residues in the RGG-motif and that of the phosphorylation sites in the RRM domain of Sbp1 did not affect the growth defect phenotype. Deletion of another eIF4G1-binding RGG-motif protein Scd6 does not affect the ability of Sbp1 to cause growth defect. Moreover, absence of Sbp1 did not affect the growth defect phenotypes observed upon overexpression of decapping activators Dhh1 and Pat1. Strikingly deletion of both the RRM domains (RRM1 and RRM2) and not the RNP motifs within them compromised the growth defect phenotype. Sbp1 mutant lacking both RRM1 and RRM2 was highly defective in localizing to RNA granules. Conclusion: This study identifies an important role of RRM domains independent of RNP motif in Sbp1 repression activity.

APA, Harvard, Vancouver, ISO, and other styles

45

Wood, Megan P., Angela Hollis, Ashley L. Severance, Megan L. Karrick, and Jennifer A. Schisa. "RNAi Screen Identifies Novel Regulators of RNP Granules in the Caenorhabditis elegans Germ Line." G3: Genes|Genomes|Genetics 6, no. 8 (June 17, 2016): 2643–54. http://dx.doi.org/10.1534/g3.116.031559.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Ivanov, P. A., and E. S. Nadezhdina. "Stress granules: RNP-containing cytoplasmic bodies arising in stress: Structure and mechanism of organization." Molecular Biology 40, no. 6 (December 2006): 844–50. http://dx.doi.org/10.1134/s0026893306060021.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Gallois-Montbrun, Sarah, Beatrice Kramer, Chad M. Swanson, Helen Byers, Steven Lynham, Malcolm Ward, and Michael H. Malim. "Antiviral Protein APOBEC3G Localizes to Ribonucleoprotein Complexes Found in P Bodies and Stress Granules." Journal of Virology 81, no. 5 (December 13, 2006): 2165–78. http://dx.doi.org/10.1128/jvi.02287-06.

Full text

Abstract:

ABSTRACT Members of the APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1-like) family of cytidine deaminases inhibit host cell genome invasion by exogenous retroviruses and endogenous retrotransposons. Because these enzymes can edit DNA or RNA and potentially mutate cellular targets, their activities are presumably regulated; for instance, APOBEC3G (A3G) recruitment into high-molecular-weight ribonucleoprotein (RNP) complexes has been shown to suppress its enzymatic activity. We used tandem affinity purification together with mass spectrometry (MS) to identify protein components within A3G-containing RNPs. We report that numerous cellular RNA-binding proteins with diverse roles in RNA function, metabolism, and fate determination are present in A3G RNPs but that most interactions with A3G are mediated via binding to shared RNAs. Confocal microscopy demonstrated that substantial quantities of A3G localize to cytoplasmic microdomains that are known as P bodies and stress granules (SGs) and are established sites of RNA storage and metabolism. Indeed, subjecting cells to stress induces the rapid redistribution of A3G and a number of P-body proteins to SGs. Among these proteins are Argonaute 1 (Ago1) and Argonaute 2 (Ago2), factors that are important for RNA silencing and whose interactions with A3G are resistant to RNase treatment. Together, these findings reveal that A3G associates with RNPs that are found throughout the cytosol as well as in discrete microdomains. We also speculate that the interplay between A3G, RNA-silencing pathways, and cellular sites of RNA metabolism may contribute to A3G's role as an inhibitor of retroelement mobility and as a possible regulator of cellular RNA function.

APA, Harvard, Vancouver, ISO, and other styles

48

Fritz, Melanie, Jens Vanselow, Nadja Sauer, Stephanie Lamer, Carina Goos, T. Nicolai Siegel, Ines Subota, Andreas Schlosser, Mark Carrington, and Susanne Kramer. "Novel insights into RNP granules by employing the trypanosome's microtubule skeleton as a molecular sieve." Nucleic Acids Research 43, no. 16 (July 17, 2015): 8013–32. http://dx.doi.org/10.1093/nar/gkv731.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Jonas, S., and E. Izaurralde. "The role of disordered protein regions in the assembly of decapping complexes and RNP granules." Genes & Development 27, no. 24 (December 15, 2013): 2628–41. http://dx.doi.org/10.1101/gad.227843.113.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Rojas, Marta, George W. Farr, Cesar F. Fernandez, Laura Lauden, John C. McCormack, and Sandra L. Wolin. "Yeast Gis2 and Its Human Ortholog CNBP Are Novel Components of Stress-Induced RNP Granules." PLoS ONE 7, no. 12 (December 21, 2012): e52824. http://dx.doi.org/10.1371/journal.pone.0052824.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Granules RNP'

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