Tesis sobre el tema "Ribosomal biogenesis"
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Verma, Pali. "The Role of NOL6 in Ribosomal Biogenesis". Thesis, Griffith University, 2015. http://hdl.handle.net/10072/365847.
Texto completoThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Eskitis Institute for Cell and Molecular Therapies
Science, Environment, Engineering and Technology
Full Text
Gartmann, Marco. "Structural characterization of ribosomal complexes involved in ribosome biogenesis and protein folding". Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-120476.
Texto completoRamesh, Madhumitha. "Analysis of Ribosome Biogenesis from Three Standpoints: Investigating the Roles of Ribosomal RNA, Ribosomal Proteins and Assembly Factors". Research Showcase @ CMU, 2016. http://repository.cmu.edu/dissertations/609.
Texto completoBurlacu, Elena. "Probing ribosomal RNA structural rearrangements : a time lapse of ribosome assembly dynamics". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/17072.
Texto completoGamalinda, Michael. "Ribosomal Proteins Orchestrate the Biogenesis of Eukaryotic Large Ribosomal Subunits in a Sequential Fashion". Research Showcase @ CMU, 2014. http://repository.cmu.edu/dissertations/441.
Texto completoG, C. Keshav. "Investigation of the Role of Bacterial Ribosomal RNA Methyltransferase Enzyme RsmC in Ribosome Biogenesis". Kent State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1621868567263046.
Texto completoLeplus, Alexis. "Study of factors implicated in small ribosomal subunit biogenesis under differents growth conditions". Doctoral thesis, Universite Libre de Bruxelles, 2010. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210189.
Texto completoDoctorat en Sciences
info:eu-repo/semantics/nonPublished
Kim, Sunghan. "Characterization of ribosomal S6 protein phosphorylation and possible control of ribosome biogenesis in arabidopsis cell culture". Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1072819298.
Texto completoTitle from first page of PDF file. Document formatted into pages; contains xvi, 147 p.; also includes graphics. Includes bibliographical references (p. 128-147).
MIYOSHI, Masaya, Tetsuya OKAJIMA, Tsukasa MATSUDA, Michiko N. FUKUDA y Daita NADANO. "Bystin in human cancer cells : intracellular localization and function in ribosome biogenesis". Biochemical Society, 2007. http://hdl.handle.net/2237/9306.
Texto completoZakari, Musinu. "The SMC loader Scc2 promotes ncRNA biogenesis and translational fidelity in Saccharomyces cerevisiae". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066148/document.
Texto completoThe Scc2-Scc4 complex is essential for loading the cohesin complex onto DNA. Cohesin generates cohesion between sister chromatids, which is critical for chromosome segregation. Scc2 (also known as NIPBL) is mutated in patients with Cornelia de Lange syndrome, a multi-organ disease characterized by developmental defects in head, limb, cognition, heart, and the gastrointestinal tract. How mutations in Scc2 lead to developmental defects in patients is yet to be elucidated. One hypothesis is that the binding of Scc2/cohesin to different regions of the genome will affect transcription. In budding yeast, Scc2 has been shown to bind to RNA Pol III transcribed genes (tRNAs, and spliceosomal), as well as RNA Pol II-transcribed genes encoding small nuclear and nucleolar RNAs (snRNAs and snoRNAs) and ribosomal protein genes. Here, we report that Scc2 is important for gene expression. Scc2 and the transcriptional regulator Paf1 collaborate to promote the production of Box H/ACA snoRNAs which guide pseudouridylation of RNAs including ribosomal RNA. Mutation of Scc2 was associated with defects in the production of ribosomal RNA, ribosome biogenesis, and splicing. While the scc2 mutant does not have a general defect in protein synthesis, it shows increased frameshifting and reduced internal ribosomal entry site (IRES) usage/cap-independent translation. These findings suggest Scc2 normally promotes a gene expression program that supports translational fidelity. We hypothesize that translational dysfunction may contribute to the human disorder Cornelia de Lange syndrome, which is caused by mutations in Scc2
FUKUDA, Michiko N., Masaya MIYOSHI y Daita NADANO. "The role of bystin in embryo implantation and in ribosomal biogenesis". Springer, 2007. http://hdl.handle.net/2237/9027.
Texto completoDas, Priyanka. "Study of the L13a residues required for ribosomal function". Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1331762160.
Texto completoWeaver, Paul L. "Characterization of a putative RNA helicase, Dbp3p, in ribosomal RNA processing and ribosome biogenesis in Saccharomyces Cerevisiae /". The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu148794750113696.
Texto completoCastle, Cathy Lynn. "Protein-Protein interactions involved in the biogenesis of eukaryotic small ribosomal subunits". Thesis, Montana State University, 2008. http://etd.lib.montana.edu/etd/2008/castle/CastleC1208.pdf.
Texto completoTobin, Christina. "Removal and Replacement of Ribosomal Proteins : Effects on Bacterial Fitness and Ribosome Function". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-150401.
Texto completoHeuer, André [Verfasser] y Roland [Akademischer Betreuer] Beckmann. "The eukaryotic small ribosomal subunit in the context of translational recycling and ribosome biogenesis / André Heuer ; Betreuer: Roland Beckmann". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1171705166/34.
Texto completoKshetri, Man B. "N-TERMINAL DOMAIN OF rRNA METHYLTRANSFERASE ENZYME RsmC IS IMPORTANT FOR ITS BINDING TO RNA AND RNA CHAPERON ACTIVITY". Kent State University Honors College / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1621007414429417.
Texto completoJanas, Maja. "Novel Regulation of MicroRNA Biogenesis and Function". Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10121.
Texto completoDator, Romel P. "Characterization of Ribosomes and Ribosome Assembly Complexes by Mass Spectrometry". University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382373082.
Texto completoInder, Kerry y n/a. "The Functional Role of NRAP in the Nucleolus". Griffith University. School of Biomolecular and Biomedical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070201.133347.
Texto completoInder, Kerry. "The Functional Role of NRAP in the Nucleolus". Thesis, Griffith University, 2006. http://hdl.handle.net/10072/367738.
Texto completoThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
Ho, Hei Ngam Jennifer. "Functional characterization of yeast NMD3 in the biogenesis and transport of the large (60S) ribosomal subunit /". Full text (PDF) from UMI/Dissertation Abstracts International, 2000. http://wwwlib.umi.com/cr/utexas/fullcit?p3004287.
Texto completoHerdman, Chelsea. "Relative roles of UBF and RRN3 in the transcription of the ribosomal RNA genes and ribosome biogenesis determined using in vivo mouse models". Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/28387.
Texto completoRibosome biogenesis, or the synthesis of ribosomes, is an important cell process occurring in the nucleolus that utilizes transcription by all three nuclear RNA polymerases. The initial and rate-limiting step is the transcription of the catalytic ribosomal RNAs 28S, 18S and 5.8S in the form of a precursor ribosomal RNA (pre-rRNA/47S) by RNA polymerase I (RPI, also known as Pol1 and POLR1). RPI has a dedicated set of basal factors responsible for its activation. These are the architectural factor UBF, the TBP containing factor SL1, the initiation factor RRN3, and the termination factor TTF1. Ribosomal RNA synthesis is tightly regulated and accounts for 30-50% of total gene transcription. As such, this process is linked to cell growth, transformation, proliferation and the actions of tumour suppressors and oncogenes. Notably, UBF and RRN3 are activated by many of the same growth signaling pathways. The human and mouse haploid genome contain ~200 copies of the ribosomal RNA genes, the ribosomal DNA (rDNA). These ribosomal DNA copies are arranged in tandem repeats on the short arms of acrocentric chromosomes. Interestingly, only a fraction of the rDNA copies are active, and a significant number are epigenetically silenced and heterochromatic. The reason for having so many copies and their regulation in vivo by silencing is not yet understood, though it has been connected with genome stability. This thesis presents the analysis of the in vivo requirements for UBF and RRN3 in rRNA transcription and rDNA chromatin structure. We had previously analyzed the loss of UBF in mouse embryonic fibroblasts using tamoxifen-dependent conditional knockout. As we wanted to compare the loss of RRN3 in a similar model, we re-analyzed the RRN3 knockout mice and created cell lines as was performed for the UBF knockout. Importantly, we find that RRN3 is essential for preimplantation and its loss arrests development at E3.5, contrary to previous work that showed a late E9.5 developmental arrest. Using mouse embryonic fibroblast (MEF) cell lines conditional for UBF or RRN3, we found that the loss of either factor prevented RPI transcription. However, we found that UBF was essential for the recruitment of the other RPI transcription factors and the formation of the preinitiation complex, as well as to maintain an open rDNA chromatin structure, while RRN3 was required only for RPI recruitment. These studies allowed us to identify an upstream boundary element on the rDNA formed of H2A.Z, TTF1, CTCF and activating histone marks, which is independent of RPI activity. We also found that UBF loss, but not RRN3 loss, led to a synchronous and massive p53-independent apoptosis, specifically in oncogenically transformed cells. This strongly suggests that drug targeting UBF could be a viable cancer treatment. Finally, we have observed that the rDNA activity status in pluripotent cells differs from that of differentiated cells. Embryonic stem cells (ESCs) were also generated from the mice conditional for UBF and RRN3. Preliminary results indicate that, unlike somatic cells, all the rRNA genes in these and other pluripotent cell lines are potentially active. This makes ESCs and their differentiation an ideal model in which to study the establishment of rDNA silencing and the role of UBF and/or RRN3 in this process. Together these data define the in vivo roles of UBF and RRN3 in ribosomal RNA transcription and suggest mechanisms by which they maintain rDNA integrity and may drive cell differentiation.
Kirby, Tyler. "GLOBAL-SCALE ANALYSIS OF THE DYNAMIC TRANSCRIPTIONAL ADAPTATIONS WITHIN SKELETAL MUSCLE DURING HYPERTROPHIC GROWTH". UKnowledge, 2015. http://uknowledge.uky.edu/physiology_etds/22.
Texto completoTiku, Varnesh [Verfasser], Adam [Gutachter] Antebi y Matthias [Gutachter] Hammerschmidt. "Small Nucleoli and Reduced Ribosomal Biogenesis are Hallmarks of Longevity / Varnesh Tiku ; Gutachter: Adam Antebi, Matthias Hammerschmidt". Köln : Universitäts- und Stadtbibliothek Köln, 2016. http://d-nb.info/1136077839/34.
Texto completoSchumacher, Heiko Tobias [Verfasser]. "Involvements of the Plant 3'-5' Exonuclease ERL1 in Chloroplast Ribosomal RNA Biogenesis and RNA Silencing Pathways / Heiko Tobias Schumacher". Kassel : Universitätsbibliothek Kassel, 2009. http://d-nb.info/999715232/34.
Texto completoBanerjee, Daipayan. "CHARACTERIZATION OF G-PATCH MOTIF CONTRIBUTION TO PRP43 FUNCTION IN THE PRE-MESSENGER RNA SPLICING AND RIBOSOMAL RNA BIOGENESIS PATHWAYS". UKnowledge, 2013. http://uknowledge.uky.edu/biology_etds/10.
Texto completoTrinquier, Aude. "Coupling between transfer RNA maturation and ribosomal RNA processing in Bacillus subtilis". Thesis, Université de Paris (2019-....), 2019. http://www.theses.fr/2019UNIP7066.
Texto completoCellular protein synthesis both requires functional ribosomes and mature transfer RNAs (tRNAs) as adapter molecules. The ribosomes are large essential ribonucleoprotein complexes whose biogenesis accounts for most of cellular transcription and consumes a major portion of the cell’s energy. Ribosome biogenesis is therefore tightly adjusted to the cellular needs and actively surveilled to rapidly degrade defective particles that could interfere with translation. Interestingly, tRNAs and ribosomal RNAs (rRNAs) are both transcribed from longer primary transcripts and universally require processing to become functional for translation. In this thesis, I have characterized a coupling mechanism between tRNA processing and ribosome biogenesis in the Gram-positive model organism Bacillus subtilis. Accumulation of immature tRNAs during tRNA maturase depletion, specifically abolishes 16S rRNA 3’ processing by the endonuclease YqfG/YbeY, the last step in small ribosomal subunit formation. We showed that this maturation deficiency resulted from a late small subunit (30S) assembly defect coinciding with changes in expression of several key 30S assembly cofactors, mediated by both transcriptional and post-transcriptional effects. Interestingly, our results indicate that accumulation of immature tRNAs is sensed by the stringent factor RelA and triggers (p)ppGpp production. We showed that (p)ppGpp synthesis and the accompanying decrease in GTP levels inhibits 16S rRNA 3’ processing, most likely by affecting GTPases involved in ribosome assembly. The inhibition of 16S rRNA 3’ processing is thought to further lead to degradation of partially assembled particles by RNase R. Thus, we propose a model where RelA senses temporary slow-downs in tRNA maturation and this leads to an appropriate readjustment of ribosome biogenesis. This coupling mechanism would maintain the physiological balance between tRNAs and rRNAs, the two major components of the translation machinery
Punekar, Avinash S. "Ribosomal RNA Modification Enzymes : Structural and functional studies of two methyltransferases for 23S rRNA modification in Escherichia coli". Doctoral thesis, Uppsala universitet, Struktur- och molekylärbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212394.
Texto completoSaby, Manon Juliette. "Identification de gènes candidats pour l'anémie de Blackfan-Diamond et caractérisation phénotypique". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/SABY_Manon_va2.pdf.
Texto completoDiamond-Blackfan anemia (DBA) is a congenital rare erythroblastopenia due to a blockage in the maturation of erythroid cells between the BFU-e and CFU-e stages. DBA is characterized by an aregenerative, usually macrocytic, anemia, associated with the total absence or less than 5% of erythroid precursors in the bone marrow. In 50% of DBA cases, anemia is associated with congenital malformations affecting the cephalic area and the extremities of the limbs and a growth delay. The DBA phenotype and genotype are heterogeneous, however a mutation in a ribosomal protein (RP) gene, always at heterozygous state, is found in 80% of cases. Up to date, 20 RP genes have been associated with DBA pathophysiology, establishing DBA as the first identified ribosomopathy. Mutations of these RP induce a defect in rRNA maturation. Therefore, for ribosome dysfunction, cell cycle arrest and p53-mediated apoptosis induction are responsible for erythroblastopenia in patients. More rarely, DBA may be the consequence of mutations present on a non-PR gene: the GATA-1 gene (major transcription factor of erythropoiesis), the TSR2 gene (interacting with the RPS26 protein and involved in ribosome biogenesis) or the EPO gene (erythropoiesis key cytokine) have been identified so far. However, 20% of the DBA patients are still not genotypically diagnosed, leaving room for the discovery of new candidate genes. In this perspective, the aim of my PhD was therefore to identify new candidate genes involved in DBA etiology and characterize their functional roles of in order to confirm their link with DBA. For this purpose, we sequenced exomes on 25 families and identified 8 candidate genes. In this manuscript, I will present my work as part of a bigger project to validate four new genes involved in BDA pathophysiology.RPL9 is a RP of the large 60S ribosomal subunit. Mutations in this gene lead to two different phenotypes depending on the allelic variant: a DBA phenotype for an allelic variant of the 5' UTR or a phenotype associated with a cancer risk. As part of a collaborative work that compared the two RPL9 variants, I showed that the DBA variant only has an impact on erythroid differentiation Compared to a healthy individual, patients presenting the DBA variant exhibit a reduced proliferation rate and a delay in the acquisition of erythroid markers. P53-dependent activation of p21 in those cells is most likely responsible for the cell cycle arrest. Activation of caspases sign an induction of apoptosis and is consistent with the reduced viability of erythroid progenitors. A collaborative study on the RPL13 gene confirmed the specific role of certain RP proteins in non-DBA diseases and added a new disease to the list of ribosomopathiesXRibosome chaperone proteins represent a new group of genes that may be associated with DBA. I investigated the proliferation, division, amplification, differentiation and viability of primary erythroid cells from patients with allelic variations in one of these genes: HEATR3. These experiments revealed a lack of erythroid proliferation, with a defect in cell division. The mRNA and protein quantifications showed a stabilization of p53, leading to an activation of its targets: p21, controlling cell cycle, and Bax, involved in apoptosis induction. We also observed a delay in differentiation with the persistence of CD34 and IL-3R immaturity markers and a delay in the appearance of terminal markers such as BAND3 or alpha4-integrin. The role of HSP70 controlling GATA1 localization in early stages of the erythroid differentiation was recently elucidated. In this work, I identified as a new candidate gene for DBA, a HSP70 family member, HSPA14, and I characterized the defects in erythroid differentiation induced by this variant. Furthermore, I was able to identify an association of DBA with a variant in CECR1 gene encoding an adenosine deaminase in several families of the EURODBA consortium
Larburu, Natacha. "Etude structurale de la biogenèse de la petite sous-unité ribosomique humaine par cryo-microscopie électronique et analyse d'images". Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30336/document.
Texto completoRibosome biogenesis is a complex process that requires the production and the correct assembly of the 4 rRNAs with 80 ribosomal proteins. In Human, the production of the two subunits, 40S and 60S, is initiated by the transcription of a pre-ribosomal rRNA precursor to the mature 18S, 5.8S, and 28S rRNAs by the RNA polymerase I, which is chemically modified and trimmed by endo- and exoribonuclease, in order to form the mature rRNAs. The nascent pre rRNA associated with ribosomal proteins, small ribonucleoprotein particles (snoRNP) and so called co-factors leading to the assembly of an initial 90S particle. This particle is then split into pre-40S and pre-60S pre-ribosomal particles that fallow independent maturation to form the mature subunit into the cytoplasm. Production of eukaryotic ribosomes implies the transient intervention of more than 200 associated proteins and ribonucleoprotein particles, that are absent from the mature subunits. Synthesis of ribosome, globally conserved in eukaryotes, has been principally studied in yeast. However, recent studies reveal that this process is more complex in human compared in yeast. An important bottleneck in this domain is the lack of structural data concerning the formation of intermediate ribosomal subunits to understand the function of assembly factors. Determination of the structural remodeling of pre-ribosomal particles is crucial to understand the molecular mechanism of this complex process. So I have undertaken a structural study on the assembly of the small ribosomal subunit using cryo-electron microscopy and image analysis. The goal of my thesis is to determine the 3D structures of human pre-40S particles at different maturation stages to see the structural remodeling that occurs during the biogenesis of the small ribosomal subunit. We are collaborating with the group of Pr Ulrike Kutay at ETH Zurich, who purify human pre-40S particles. The 3D structures of human pre-40S particles purified at an intermediate and late maturation stages, has been determined with a resolution of 19 and 15Å respectively. Supplementary densities, compared to the mature subunit, indicate the presence of assembly factors and show the unexpected presence of the RACK1 protein in the precursor of the human small ribosomal subunit in the cytoplasm. The comparison of the 3D structures of human pre-40S particle allows showing the structural remodeling that occur during the maturation of the small ribosomal subunit. This work provides the first 3D structure of human pre-40S particles and laid the methodological foundations for future exploration of the structural dynamics of pre-ribosomal particles
Quynh, Tran Hoang Thi. "Identification and functional characterization of trans-acting factors required for eukaryotic ribosome synthesis". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210540.
Texto completoIn the budding yeast Saccharomyces cerevisiae, it has been reported recently that the processing of the 35S nascent transcript and the assembly of pre-ribosomes occur concomitantly with Pol I transcription in the nucleolus. In this process, the growing Pol I transcript gradually assembles with pre-40S structural ribosomal proteins and ribosomal synthesis factors to form the so-called ‘SSU-processome’ or ‘90S pre-ribosome’, the earliest precursor of the 40S subunit. The SSU-processome/90S pre-ribosome localizes to the nucleolus and consists of the 35S pre-rRNA, the U3 small nucleolar (sno) RNA, about a dozen of 40S ribosomal proteins and more than forty ribosome synthesis factors. The U3 snoRNA and pre-40S ribosome synthesis factors are all implicated in the processing of the 35S precursor (at sites A0, A1 and A2) and therefore in the synthesis of the 18S rRNA component of the 40S subunit. Significantly, the association of the U3 snoRNA with the growing 35S transcript is important for pre-40S assembly, whereas its dissociation from the processed transcript (following cleavage at sites A0-A2) is crucial for the overall structural remodeling of the 18S rRNA and for the formation of pre-40S ribosomes from the earliest precursor 90S particles.
This thesis mostly addresses the identification and functional characterization of Esf2 and Bfr2, two novel 40S synthesis factors, components of the SSU-processome/90S pre-ribosome in yeast. Both proteins localize to the nucleolus and their genetic depletions lead to failure in the production of 40S subunits. In the absence of either factor, the 35S pre-rRNA is not processed at sites A0-A2 and the 18S rRNA is not synthesized. Also, pre-ribosome assembly is affected and pre-40S ribosomes fail to mature properly. Strikingly, in the absence of either factor, the U3 snoRNA remains associated with unprocessed 35S transcript within pre-ribosomes indicating that Esf2 and Bfr2 are required to dissociate U3 from pre-ribosomes. This process also involves RNP (ribonucleoprotein particle) unwinding activities of the putative RNA helicase Dbp8.
La biogenèse du ribosome eucaryote est un processus complexe qui consomme beaucoup d’énergie et implique plusieurs centaines de facteurs trans qui s’associent de manière transitoire avec les pré-ribosomes en cours de formation. La biogenèse des sous-unités ribosomiques (la petite sous-unité 40S et la grande sous-unité 60S) débute dans le nucléole par la synthèse d’un long précurseur d’ARN ribosomique (le pré-ARNr, dit 35S chez la levure Saccharomyces cerevisiae) par l’ARN Polymérase I (Pol I). Ceci constitue une étape clé dans le contrôle global de la synthèse du ribosome chez la levure. Le pré-ARNr 35S renferme les séquences des ARNr matures 18S (ARNr de la sous-unité 40S) et 5.8S et 25S (deux des trois ARNr de la sous-unité 60S). Le pré-ARNr 35S subit un long processus de maturation et d’assemblage au cours duquel il est modifié, clivé (on parle du « processing » du pré-ARNr) et s’assemble avec des protéines ribosomiques (« RP », composants structuraux des sous-unités ribosomiques matures) et de nombreux facteurs de synthèse (facteurs trans) pour former différentes particules pré-ribosomiques (précurseurs des sous-unités 40S et 60S).
Chez la levure S. cerevisiae, il a récemment été montré que le processing du pré-ARNr 35S et l’assemblage des pré-ribosomes se produisent de manière concomminante avec la transcription Pol I dans le nucléole. Ainsi, le transcrit Pol I en cours de synthèse s’assemble progressivement avec des facteurs de synthèse ainsi que des RP pour former le « SSU processome » ou « pré-ribosome 90S », tout premier précurseur de la petite sous-unité 40S. Le SSU processome/pré-ribosome 90S est localisé dans le nucléole et est consisté du pré-ARNr 35S naissant, du petit ARN nucléolaire (snoRNA) U3, d’une douzaine de RP de la petite sous-unité 40S et de plus de 40 facteurs de synthèse. Le snoRNA U3 et ces facteurs de synthèse sont tous impliqués dans les clivages du pré-ARNr 35S aux sites A0, A1 et A2, et donc dans la biogenèse de l’ARNr 18S. L’association du snoRNA U3 avec le pré-ARNr 35S naissant est importante pour l’assemblage du SSU processome/pré-ribosome 90S. Par ailleurs, sa dissociation après les clivages aux sites A0-A2 permet un remodelage structural général de l’ARNr 18S et la formation du « pré-ribosome 40S » à partir de la particule précoce 90S.
Au cours de cette thèse, nous avons identifié et caractérisé fonctionnelement chez la levure deux nouveaux facteurs de synthèse de la petite sous-unité 40S et composants du SSU processome/pré-ribosome 90S: Esf2 et Bfr2. Ces deux protéines sont localisées dans le nucléole. Leur déplétion entraîne une incapacité à produire la sous-unité ribosomique 40S. En l’absence d’Esf2 ou Bfr2, le pré-ARNr 35S n’est plus clivé aux sites A0-A2 et l’ARNr 18S mature n’est plus produit. L’assemblage des pré-ribosomes est aussi affecté, notamment la formation du pré-ribosome 40S. De manière importante, en l’absence de l’un ou l’autre de ces facteurs, le snoRNA U3 reste associé au pré-ARNr 35S non clivé au sein des pré-ribosomes, indiquant qu’Esf2 et Bfr2 sont requises pour la dissociation d’U3 des pré-ribosomes. Ce processus implique aussi Dbp8, une hélicase à ARN présumée.
Doctorat en sciences, Spécialisation biologie moléculaire
info:eu-repo/semantics/nonPublished
Bouffard, Stéphanie. "Study of ribosome biogenesis factors in zebrafish neural progenitors". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS228/document.
Texto completoWhile ribosome biogenesis has been consideredas an ubiquitous mechanism, steps of thisprocess have recently been shown to be tissuespecific. Zebrafish optic tectum (OT) is asuitable model to study cell proliferation sincecells at different differentiation states arespatially partitioned.During my PhD, I examined whether ribosomebiogenesis genes may have specific roles inneuroepithelial progenitor cells (NePCs).Taking advantage of a previous transcriptomicanalysis, I first screened for new candidatesaccumulated in NePCs. I decided to focus onproliferation-associated 2G4 (pa2g4/ebp1),which was expressed preferentially in NePCs.This gene promotes or represses cellproliferation in normal organisms or duringtumorigenesis. I designed a strategy for theinducible expression and cell specificexpression of this gene.Fibrillarin (Fbl), a small nucleolarmethyltransferase is also preferentiallyexpressed in NePCs. It plays an important rolein cancer. I showed that fbl mutants displayedspecific OT defects linked to a massiveapoptosis and an absence of neuraldifferentiation. I also demonstrated deficienciesin the ribosome translational activity.Additionally, fbl mutants showed impaired Sphaseprogression. Our data suggest that fbl isessential for the proliferation of zebrafishneuronal progenitors
Deraze, Jérôme. "Epigenetic control of ribosome biogenesis homeostasis". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066342/document.
Texto completoTranslation is an essential metabolic activity carried by ribosomes. These complexes are synthetized in the nucleolus, and require the coordinated expression of 4 ribosomal RNA, 80 ribosomal proteins, and more than 200 assembly factors. Indeed, their biogenesis is complex and expensive, consuming more than half of the energy in proliferating cells. As the cellular need for ribosomes varies with environmental or metabolic conditions, their synthesis is tightly regulated in response to a number of cues. Many mechanisms ensure that the intensity of ribosome biogenesis is coupled to cell homeostasis. Such is the ability of ribosomal proteins to regulate gene expression at many levels, from translation specificity to activation or repression of transcription. Many such functions are carried off the ribosome, and are thus termed extraribosomal. Our team discovered a new extraribosomal function of ribosomal protein uL11 in Drosophila. Indeed, when trimethylated on lysine 3 (uL11K3me3), it associates with Corto, a transcription factor of the Enhancers of Trithorax and Polycomb family. By studying their genome-wide binding profile on chromatin, we show that these proteins are distributed along different patterns, and that uL11K3me3 specifically binds a subset of active genes enriched in ribosome biogenesis components. Additionally, we generated the first genetic alleles for Drosophila uL11 and describe the molecular screening method that we employed. Last, we studied the uL11 alleles that delete or replace lysine 3. We describe that their Minute-like phenotypes suggest an essential role for the N-terminal domain of uL11, though it may be independent of its association with Corto
Therizols, Gabriel. "Rôle des ribosomes et de leur biogenèse dans la tumorigenèse et la réponse aux traitements chimiothérapeutiques". Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10083/document.
Texto completoCancer cells produce large amounts of ribosomes to synthesize the proteins required for their rapid proliferation. The mechanisms leading to this increase in ribosome production are only partly understood, but they are related to the acquisition of the tumor phenotype. In addition, a new theory proposes that ribosomes are not neutral effectors of translation, but have a direct role in the regulation of gene expression. This theory is based on the observation that ribosome composition is heterogeneous in different cell types and according to environmental conditions. In this context, I have analyzed the relationships between changes in signals that control ribosome biogenesis, both quantitatively and qualitatively, and the development of the tumor phenotype. This manuscript reports three studies made during this PhD program. These studies identified: i) a novel regulator of the amount of ribosomes, the LN-Netrin-1 and ii) changes in the ribosome composition and function induced by genetic alterations (loss of activity of p53) and by the use of a chemotherapeutic molecule, the 5-Fluorouracil. These perturbations of the amount and the function of ribosomes modify the translation control and cell growth, cell proliferation and cell survival. From these results it can be conclude that ribosomes are elements involved in the regulation of gene expression and play a role in cancer pathology and response to chemotherapy
Sloan, Katherine. "The exosome and human ribosome biogenesis". Thesis, University of Newcastle Upon Tyne, 2012. http://hdl.handle.net/10443/1462.
Texto completoJarzebowski, Léonard. "Unraveling variations in ribosome biogenesis activity in the mouse hematopoietic system at homeostasis in vivo". Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066402/document.
Texto completoStem cells (SCs) differ from progenitors and differentiated cells on many aspects. Notably, SCs display particular characteristics in fundamental cellular processes, and ribosome biogenesis (RiBi) has recently been proposed to play an important role in the regulation of SCs. During my thesis, I have used various approaches to study the role and regulation of RiBi in SC populations, using in vivo and ex vivo mouse models.Using genetic inactivation of the RiBi factor Notchless (Nle), I have participated to the analysis of its role in the adult hematopoietic system and intestinal epithelium, and in the establishment of the first cell lineages during early embryogenesis. In vivo, constitutive Nle deficiency causes early embryonic lethality, and I showed ex vivo that Nle inactivation in embryonic SCs induces a ribosomal stress response mediated by the tumor suppressor p53, and proliferation/survival defects. Conditional Nle inactivation in the adult mouse also induces activation of p53 in hematopoietic and intestinal SCs in vivo, leading to their rapid elimination.In parallel, I have used different methods to analyze the RiBi activity of hematopoietic SCs (HSCs) and immature progenitors at homeostasis, in vivo in the adult mouse. Thus, I have unraveled variations in the RiBi activity of these populations, and notably uncovered previously unsuspected RiBi activity in HSCs despite their quiescent state.Altogether, my work supports the hypothesis of a role for RiBi in the regulation of SCs and provides better understanding of the activity of this process during hematopoietic differentiation
D'Souza, Aaron Raynold. "Protein factors involved in the biogenesis of the mitochondrial ribosome". Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273764.
Texto completoLee, Chrissie Young. "Multiple mechanisms regulating ribosome biogenesis in Saccharomyces cerevisiae". Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1781954291&sid=2&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Texto completoSaraf, Kritika. "Functional characterization of the connections between translation and ribosome biogenesis". Doctoral thesis, Universite Libre de Bruxelles, 2019. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/288480.
Texto completoLes ribosomes sont des nanomachines cellulaires responsables de la production de protéines dans toutes les cellules vivantes. Lorsque la biogenèse des ribosomes est compromise ou que la fonction des ribosomes est infidèle, elle provoque des maladies appelées ribosomopathies. L'objectif principal de ma thèse était de comprendre les conséquences du dysfonctionnement de la biogenèse des ribosomes sur la traduction. J'ai contribué à cette compréhension par le biais de quatre projets différents visant à comprendre comment la fonction des ribosomes affecte les différentes étapes de la traduction des protéines dans la cellule. Dans mon premier projet, nous avons voulu determiner si une méthylation sur l’ARN ribosomique d’un sucre présente sur la grande sous-unité ribosomique joue un rôle dans la traduction. Nous avons constaté que la perte de cette modification n'inhibait pas grossièrement la production ou la croissance des ribosomes. Cependant, ces mutants sont résistants à G418 et font moins d’erreurs de décodage par rapport aux cellules contrôles. Dans mon deuxième projet, j'ai étudié une méthyltransférase appelée Mtq2, qui méthyle le facteur de libération de la terminaison de la traduction, eRF1. Nous avons constaté que Mtq2 est directement impliqué dans les dernières étapes de la maturation des grandes sous-unités ribosomiques et que l'activité catalytique de Mtq2 est nécessaire pour une production efficace de sous-unités 60S et pour une exportation antérieure à 60S. Dans le cadre du projet 3, j'ai étudié un alcaloïde naturel d'origine végétale appelé hémanthamine (HAE). Nous avons montré que HAE lie le centre de la peptidyl transférase de la grande sous-unité du ribosome eucaryote, où il interagit avec l'ARNr 25S. Nous avons également montré que HAE inhibe les stades précoces du traitement pré-ARNr et induit une réponse au stress nucléolaire dans les cellules. Dans le projet 4, j'ai étudié un long ARN non codant appelé SAMMSON. SAMMSON joue un rôle crucial dans la survie du mélanome. Nous avons constaté que sa perte d’expression affecte négativement la biogenèse des ribosomes. Nous avons également démontré qu'en modulant l'affinité de liaison d'une protéine unique, à savoir CARF, SAMMSON réarme le réseau ARN-protéine et favorise une augmentation synchronisée de la maturation de l'ARNr à la fois dans le cytosol et les mitochondries, renforçant ainsi la traduction dans les deux compartiments cellulaires.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Lackmann, Fredrik. "Nucleolar Ribosome Assembly". Doctoral thesis, Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-145639.
Texto completoAt the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.
Brombin, Alessandro. "Functional study of the role played by nucleolar proteins in the control of neural progenitor homeostasis using zebrafish as a model". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA112237/document.
Texto completoIn neural stem cells (NSCs) and neural progenitors (NPs), as in other cell types, cell identity is characterized by specific molecular signatures that depend on the environment provided by neighboring cells. Thus, it is important to study progenitor cells in vivo. The zebrafish optic tectum (OT) is a suitable model for that purpose. Indeed, this large structure of the dorsal midbrain displays life-long oriented growth supported by neuroepithelial cells present at its periphery (in the peripheral midbrain layer, PML). Moreover, neuroepithelial progenitors, fast-amplifying progenitors and post-mitotic cells are found in adjacent domains of the OT, as a consequence of its oriented growth. Each cell population is marked by concentric gene expression patterns. Interestingly, a datamining of the ZFIN gene expression database allowed us to identify around 50 genes displaying biased expression in PML cells (neuroepithelial progenitors). Interestingly, many “PML genes” code for ribosome biogenesis factors. The accumulation of transcripts for such ubiquitously expressed genes in SAPs was very surprising so during my thesis I examined whether ribosome biogenesis may have specific roles in these neuroepithelial cells, while improving our knowledge. Indeed, although it is generally admitted that ribosome biogenesis is essential in all cells, it has been shown quite recently that several components of the ribosome biogenesis have tissue restricted roles. For example, Notchless is required for the survival of the inner cell mass in the preimplantation mouse embryo. More recently, conditional knock-out experiments in mice showed that Notchless is necessary for the maintenance of hematopoietic stem cells and intestinal stem cells, but not for committed progenitors and differentiated cells. Indeed in the absence of Notchless in stem cells, the immature 60S subunit cannot be exported from the nucleus and accumulates. This does not happen in differentiated cells where Notchless is dispensable. I started a functional study based on the conditional overexpression of a dominant-negative form of the gene notchless homolog 1 (nle1, the zebrafish homolog of the mammalian gene Notchless). My hypothesis was that the PML slow-amplifying progenitors (SAPs) may require Notchless for the maturation of the 60S subunit, but not the differentiated cells which could survive also after the deletion of this gene. Experiments are still underway. So far we could demonstrate that nle1 has a crucial role in SAPs. I studied zebrafish mutants for genes coding for the components of the box C/D small nucleolar ribonucleoprotein (snoRNP) complex (Fibrillarin, Nop56, Nop58). Mutants displayed a similar phenotype with massive apoptosis and a deregulation of the cell cycle in the whole tectum at 48hpf. Our data suggest a cell cycle arrest at the G2/M transition, highlighting novel possible mechanisms of cell cycle arrest upon impaired ribosome biogenesis. All together, these data highlight how ribosome biogenesis factors and the whole ribosome biogenesis contribute to the fine regulation of cell homeostasis thereby contributing to the determination of progenitor cell identity
Shayan, Azad Seyed Ramtin. "Analyse structurale de la biogenèse de la petite sous-unité ribosomique eucaryote par cryo-microscopie électronique et analyse d'images". Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30128.
Texto completoRibosome assembly is a complex process that requires the intervention of more than 200 assembly factors (AFs). These proteins are essential for the processing and modification of ribosomal RNAs, as well as the structural assembly of ribosomal subunits. This mechanism, highly studied in yeast, generally conserved in eukaryotes, but has become more complex with evolution in higher eukaryotes. In addition, defects in ribosome synthesis have recently been associated with a list of human genetic diseases (called ribosomopathies) and cancers, via ribosome biogenesis disease. Numerous molecular and functional studies then made it possible to define several successive stages of cytoplasmic maturation of pre-40S particles in human and yeast. It is now crucial to incorporate these highly detailed molecular descriptions of ribosome maturation events into a three-dimensional view of ribosome assembly and to understand the structural remodeling of pre-ribosomal maturation particles. Using tandem purification methods, coupled with cryo-electron microscopy and isolated particle analysis, I have determined several high-resolution 3D structures of cytoplasmic pre-40S particles, in yeast and human, at different maturation steps. First, i determined the 3D structure of the pre-40S particles, purified using AF Tsr1-FPZ as a bait at 3.1 Å resolution. Structural heterogeneity tests indicated that the beak and platform domains are dynamic zones, and sheds new light on the structural remodeling events occurring during 40S subunit assembly. Moreover, in collaboration with the team of Dr. Brigitte Pertschy, we have determined the 3D structure of yeast cytoplasmic pre-40S particles carrying point mutations on Rps20. Our atomic models have allowed to highlight a close relationship between the correct assembly of Rps20 and the release of AFs Ltv1 and Rio2 from the maturing small ribosomal subunit. Finally, I also determined the 3D structures of human pre-40S particles trapped at a very late cytoplasmic maturation step, with a resolution of ~3 Å. This work was performed in collaboration with Prof. Ulrike Kutay's team (ETH Zurich). These data allowed us to uncover new steps in the cytoplasmic maturation of human pre-40S particles. This structural study allows us to propose new molecular mechanisms underlying the final steps of eukaryotic ribosomal assembly
Cerezo, Emilie. "Contribution de la signalisation RSK à la synthèse de la petite sous-unité ribosomique humaine". Thesis, Toulouse 3, 2021. http://www.theses.fr/2021TOU30288.
Texto completoRibosome biogenesis feeds the cellular needs in protein synthesis by synthetizing translation-competent ribosomes. This highly energy-consuming process mobilizes the three RNA polymerases (Pol) and the translational machinery, active import and export through the nucleo-cytoplasmic network, as well as an intricate maturation pathway that involves more than 200 assembly and maturation factors (AMFs). In proliferating mammalian cells, the synthesis rate of ribosomes has been estimated at 7500 ribosomal subunits per minutes, requiring ~300 000 ribosomal proteins (RPs), 150 small nucleolar RNAs (snoRNAs) per pre-rRNA and an even higher number of AMFs. This fuel-consuming cellular process is tightly regulated by mechanisms that dynamically coordinate ribosome levels with cell requirements, thereby preventing energy waste due to production of unnecessary ribosomes. During my thesis, I studied discrete ribosome biogenesis regulatory events orchestrated by the Ras-MAPK/ERK signaling pathway. This signaling pathway is one of the main actor of cell growth and proliferation. ERK and its downstream effector kinase RSK stimulate three key events of ribosome biogenesis: Pol I/Pol III transcription, nucleo-cytoplasmic transport, and translation. However, no substrate of this pathway has been clearly identified in the post-transcriptional steps of ribosome biogenesis, namely ribosome assembly and maturation. My study identified the kinase RIOK2 as a new target of RSK kinase. We found that phosphorylation of RIOK2 by RSK promotes its dissociation from pre-40S particles, thereby facilitating the completion of small ribosomal subunit synthesis. Beside these findings, we have characterized the RIOK2 proximal interactome. Analysis of the proteins spatially close to RIOK2 paves the way to new connections between RIOK2, as well as other AMFs, and key intracellular processes other than ribosome biogenesis. Altogether, my thesis contributed to the discovery of novel insights into the regulation of ribosome maturation steps. Identification of novel regulatory events may help better integrating phenotypes associated with deregulation of ribosome biogenesis, during both physiological changes and diseases
Kaczanowska, Magdalena. "Study of the link between translation termination and ribosome biogenesis /". Stockholm : Institutionen för genetik, mikrobiologi och toxikologi, Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-288.
Texto completoKnight, John. "Regulation of SIRT1 protein in cancer metabolism and ribosome biogenesis". Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/2214/.
Texto completoArmistead, D. Joy. "Role of EMG1 in Bowen-Conradi syndrome and in ribosome biogenesis". The American Society of Human Genetics, 2009. http://hdl.handle.net/1993/23413.
Texto completoChoudhury, Priyanka [Verfasser]. "Functional analyses of RNA helicases in human ribosome biogenesis / Priyanka Choudhury". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1222738171/34.
Texto completoPelava, Andria. "Human ribosome biogenesis and the regulation of the tumour suppressor p53". Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3561.
Texto completoEssongue, Aurore Hélène. "Mise en évidence des réponses cellulaires indépendantes de p53 induites par l’inhibition de la biogénèse des ribosomes". Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T057/document.
Texto completoRibosome biogenesis is the process that leads to the assembly of ribosomal RNA (rRNA) and ribosomal proteins of the small (RPS) or the large (RPL) subunit into ribosomal 40S and 60S subunits. This is a highly complex process in the cells which uses a large amount of energy and resources. High rate of ribosome biogenesis is a trait of cell proliferation in physiological or pathogenic conditions. Inhibition of ribosome biogenesis activates a cell cycle checkpoint which induces a cell cycle arrest, and apoptosis. Activation of this checkpoint is due to the inhibition of ubiquitin ligase E3 MDM2, which does not anymore address the tumor suppressor factor p53 to proteasome. The p53 tumor suppressor factor then accumulates in cells and blocks the cell cycle progression. The inhibition of MDM2 is caused by the binding of a complex formed by RPL11, RPL5 and rRNA 5S. Few studies reveal that activation of this checkpoint has a therapeutic effect on cancer cells characterized by high rate of ribosome biogenesis. However, p53 activation seems to have pathogenic effects in ribosomopathies, a set of disorders characterized by ribosome biogenesis impairment, like Diamond-Balckfan macrocytic anemia (DBA). It is clear that p53 has anti-proliferative effects when ribosome biogenesis is inhibited, but evidences show that p53independants mechanisms also exist. In DBA for example, mutations in RPL5 and RPL11 that do not lead to p53 activation are observed. The goal of this study was to investigate the cellular mechanisms induced in response to inhibition of ribosome biogenesis. These investigations have been performed in an in-vitro system of cell lines. In those cell lines, ribosome biogenesis has been inhibited by depletion of RPs of the 40S or 60S ribosomal independently of p53 status. We brought out links between inhibition of ribosome biogenesis and endoplasmic reticulum homeostasis, or metabolic genes expression regulation like oncogene PHGDH