Дисертації з теми "Ribosome biogensis"
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Dator, 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.
Повний текст джерелаBurlacu, Elena. "Probing ribosomal RNA structural rearrangements : a time lapse of ribosome assembly dynamics." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/17072.
Повний текст джерелаGartmann, 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.
Повний текст джерелаZakari, Musinu. "The SMC loader Scc2 promotes ncRNA biogenesis and translational fidelity in Saccharomyces cerevisiae." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066148/document.
Повний текст джерелаThe 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
Ramesh, 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.
Повний текст джерелаTherizols, 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.
Повний текст джерелаCancer 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
G, 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.
Повний текст джерелаBouffard, Stéphanie. "Study of ribosome biogenesis factors in zebrafish neural progenitors." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS228/document.
Повний текст джерелаWhile 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.
Повний текст джерелаTranslation 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
Nguyen, Van Long Flora. "Altérations de composition des ribosomes dans les cancers du sein : analyses de cohortes humaines et modèles cellulaires." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1095/document.
Повний текст джерелаRibosomes are responsible of translating mRNAs to proteins. Alterations of ribosome composition modify its translation activity and favour tumourigenesis. Identification of ribosomes composition alterations in breast cancers might correspond to a new mechanism responsible of mammary tumourigenesis and might open up novel therapeutic approaches. Indeed breast cancers represent the first cause of women mortality due to cancers and their heterogeneity induces an important therapeutic problem.In this context, alterations of ribosomes composition were determined in human cohorts and in EMT (Epithelial to Mesenchymal Transition) cellular models, the EMT being a process involved in mammary tumourigenesis. This studies identify : (i) two factors involved in ribosome biogenesis, FBL (fibrillarin) and NCL (nucleolin) whose expression variations are associated with poor prognosis in patients and (ii) variations of ribosome composition and its translational activity in EMT. Altogether, this data support the presence of ribosomes composition alterations in breast cancers
Sloan, Katherine. "The exosome and human ribosome biogenesis." Thesis, University of Newcastle Upon Tyne, 2012. http://hdl.handle.net/10443/1462.
Повний текст джерелаKim, 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.
Повний текст джерелаTitle 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, and Daita NADANO. "Bystin in human cancer cells : intracellular localization and function in ribosome biogenesis." Biochemical Society, 2007. http://hdl.handle.net/2237/9306.
Повний текст джерелаJarzebowski, 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.
Повний текст джерелаStem 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
Leplus, 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.
Повний текст джерелаDoctorat en Sciences
info:eu-repo/semantics/nonPublished
Tobin, 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.
Повний текст джерелаWeaver, 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.
Повний текст джерелаD'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.
Повний текст джерелаGutierrez, Raissa Ferreira. "Estudos funcionais de CrNIP7 de Chlamydomonas reinhardtii: uma proteína envolvida na biogênese de ribossomos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-21102016-140046/.
Повний текст джерелаRibosome biogenesis is a complex, highly regulated and ordered process in which the primary transcript is processed by endo- and exonucleases to generate the mature ribosomal RNAs. This process was best characterized in Saccharomyces cerevisiae, but some factors have been described in humans with different function. One of these divergent factors is NIP7, a highly conserved protein in eukaryotes, which acts in the formation of ribosomal 60S subunit, in yeast, and 40S, in humans. Based on this, this work proposed the functional characterization of CrNIP7 protein, homologous to NIP7, from Chlamydomonas reinhardtii. C. reinhardtii is a green alga, ancestral to plants, that is used as an eukaryote model for photosynthesis and flagella studies. In this study, a functional complementation assay was performed using two different strains of Saccharomyces cerevisiae and, in both approaches, CrNIP7 protein complemented the function of Nip7p from yeast, indicating its participation in the synthesis of the 60S ribosomal subunit. A two-hybrid assay was carried out using CrNIP7 as bait to screen a C. reinhardtii cDNA library in order to find out CrNIP7 interaction partners, wich resulted in two novel potentially partners. The interacting proteins were identified as conceptually predicted proteins in the genome of C. reinhardtii and were called Predicted and G-patch. Additionally, the interaction between CrNIP7 and CrSBDS, a protein homologous to Sdo1 (yeast) and HsSBDS (humans), was confirmed by a direct two-hybrid assay. The interaction between CrNIP7 and CrSBDS proteins was validated by pull down and a preliminary test suggested that CrNIP7 and Predicted also interact in vitro. Bioinformatics analyzes indicate that Predicted, G-patch and CrSBDS have intrinsically disordered regions, which can be ordered in the moment of interaction. Taken together, the results of this work contribute to understand the role played by CrNIP7 in ribosome biogenesis in Chlamydomonas reinhardtii compared to other eukaryotic models.
Kshetri, 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.
Повний текст джерелаLackmann, 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.
Повний текст джерелаAt the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.
Lee, 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.
Повний текст джерелаHeuer, André [Verfasser], and 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.
Повний текст джерелаBrombin, 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.
Повний текст джерелаIn 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.
Повний текст джерелаRibosome 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.
Повний текст джерелаRibosome 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.
Повний текст джерелаKnight, John. "Regulation of SIRT1 protein in cancer metabolism and ribosome biogenesis." Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/2214/.
Повний текст джерелаSaraf, 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.
Повний текст джерелаLes 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
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Essongue, 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.
Повний текст джерелаRibosome 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
Bruelle, Marion. "Implication de la protéine de biogenèse des ribosomes Rsl24d1 dans l'homéostasie de cellules souches embryonnaires murines." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1015/document.
Повний текст джерелаEmbryonic stem cells (ESC) possess clonogenic and pluripotency abilities i.e. they are able to self-renew indefinitely in the same developpemental state and to differentiate in all the cell types composing embryonic and adult tissues. ESC homeostasis is coordinated by complex networks which are regulated at different levels of gene expression regulation, including epigenetic, transcriptional and post-transcriptional levels. Furthermore, emerging evidences point out that the translational machinery, ribosomes, are directly implicated in the control of adult and embryonic stem cell homeostasis in different model organisms. Along this line, we have identified Rsl24d1, a ribosomal associated protein (RaP), which is strongly expressed in naïve murine ESCs compared to their differentiated progenies. We demonstrated that Rsl24d1 actively contributes to ESC homeostasis and its expression is essential for ESC proliferation and clonogenic capacities. Finally, we have also demonstrated that Rsl24d1, like Rlp24 its yeast ortholog, is associated to pre-ribosomes in ESCs from the nucleus to the cytoplasm and is required for the biogenesis of the large ribosomal subunit
Armistead, 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.
Повний текст джерелаChoudhury, 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.
Повний текст джерелаPelava, 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.
Повний текст джерелаHerdman, 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.
Повний текст джерелаRibosome 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.
Dönhöfer, Alexandra [Verfasser], and Roland [Akademischer Betreuer] Beckmann. "Auxiliary factors regulating ribosome function : Roles in biogenesis, antibiotic resistance and ribosome recycling / Alexandra Dönhöfer. Betreuer: Roland Beckmann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1033752150/34.
Повний текст джерелаMcCaughan, Urszula Maria. "Characterisation of the eukaryotic ribosome biogenesis factors, Nob1, Dim2, and Tsr1, and their interactions with RNA." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/10500.
Повний текст джерелаMadru, Clément. "Étude structurale et fonctionnelle du complexe Rpf2/Rrs1 impliqué dans la biogenèse du ribosome." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB142/document.
Повний текст джерелаRibosome Biogenesis is a complex process that requires the production and the correct assembly of the 4 rRNA with more than 80 proteins. Ribosome biogenesis starts by the transcription of a pre-RNA precursor in the nucleolus. Three of the four ribosomal RNAs, the 5.8S, 18S, and 25S rRNAs, are cotranscribed as a single 35S precursor by polymerase I. This precursor is cotranscriptionally modified, folded, cleaved, and assembled with both ribosomal proteins and non-ribosomal factors to generate the mature ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S particle, containing ribosomal proteins Rpl5 and Rpl11, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53 The main objective of my thesis was to understand the precise roles of the two assembly factors Rpf2 and Rrs1 in ribosome biogenesis. These proteins have two distinctive functions : Rpf2 and Rrs1 are required for the 5S particle incorporation into the large subunit, and stimulate the rRNA transciption by polymerase I. Using a combination of structural studies by X-Ray crystallography and biochemical approaches as in vitro and in vivo methods to study proteins-RNA interactions, I was able to uncover the function of the Rpf2/Rrs1 dimer in the maturation of the large subunit through the recruitment of the 5S particle. I also studied the function of Rpf2 and Rrs1 in the rRNA transcription regulation, by characterizing physical connection with polymerase I subunits
Saby, 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.
Повний текст джерелаDiamond-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
Maouche, Samia rim. "Rôle de la petite GTPase CgtA dans la biogenèse du ribosome et la réponse au stress chez Escherichia coli." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4088.
Повний текст джерелаThe stringent response is a physiological process that occurs when bacterial cells encounter nutritional stresses, and allowing coordinated growth arrest. This conserved response is characterized by the accumulation of tetra- and pentaphosphate guanosine (ppGpp). ppGpp bind to RNA polymerase and modifies its kinetic properties, thereby affecting the transcription of many genes. Prinicpaly, ppGpp accumulation inhibits stable RNAs (rRNA and tRNA) biosynthesis, which in consequence inhibits ribosome biogenesis. Escherichia coli contains two enzymes involved in ppGpp metabolism, RelA and SpoT. During amino acid starvation, RelA bound to ribosomes produces ppGpp in response to the presence of uncharged tRNA in the ribosomal A-site. In contrast, SpoT produces ppGpp in response to other types of nutrient limitations, such as carbon starvation, but the detected signals and mechanism involved are still unknown. It has been proposed that the CgtA protein is involved in the stringent response control by interacting with SpoT at the ribosome. CgtA is a conserved and essential small GTPase of the Obg family. CgtA has also been implicated in ribosome maturation, chromosome segregation and division, but its precise function remains unknown. The cgtA gene is located downstream of rplU, rpmA and yhbE genes coding respectively for L21 and L27 proteins of the 50S subunit of the ribosome, and an integral inner membrane protein of unknown function. This genetic proximity with rplU and rpmA genes is highly conserved in bacteria. My thesis work was therefore organized around three questions. First, understanding the role of CgtA in growth control and in the stringent response
Malamoussi, Anastassia. "Peter Pan, a new link between ribosome biogenesis and cell cycle control." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-125630.
Повний текст джерелаOnofrillo, Carmine <1984>. "Ribosome Biogenesis and cell cycle regulation: Effect of RNA Polymerase III inhibition." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5422/.
Повний текст джерелаFUKUDA, Michiko N., Masaya MIYOSHI, and Daita NADANO. "The role of bystin in embryo implantation and in ribosomal biogenesis." Springer, 2007. http://hdl.handle.net/2237/9027.
Повний текст джерелаHadjeras, Lydia. "Localisation membranaire de la RNase E : rôle dans la dégradation des ARN et la biogenèse des ribosomes." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30231.
Повний текст джерелаRNase E in Escherichia coli is an essential endoribonuclease with important roles in stable RNA maturation, in ribosome quality control and in constitutive and regulated mRNA degradation. The Membrane Targeting Sequence (MTS), which forms an amphipathic α-helix, anchors RNase E on the inner cytoplasmic membrane. The absolute conservation of the MTS among -Proteobacteria suggests an important role for RNase E membrane association in RNA metabolism. To elucidate the cellular function of the membrane association of RNase E, we characterized the rne∆MTS strain expressing cytoplasmic RNase E. The results of this study lead us to propose that RNase E membrane association is necessary for RNase E stability, for functional interactions with membrane-associated regulatory factors and for protecting nascent transcripts in the nucleoid from premature interactions with RNase E. In particular, keeping RNase E to the membrane is critical for the specificity of RNase E in ribosome quality control. Membrane association is a new layer of regulation that can explain how RNase E, an enzyme with little sequence specificity and many substrates, can fulfill both ‘maturase’ and ‘degradase’ functions
Gibbs, Michelle. "Roles of conserved translational GTPases in bacterial ribosome assembly." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu158645942027837.
Повний текст джерелаDas, Priyanka. "Study of the L13a residues required for ribosomal function." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1331762160.
Повний текст джерелаRaveux, Aurélien. "In vivo exploration of the impact of ribosome biogenesis alterations on intestinal homeostasis and tumorigenesis in the adult mouse." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS517.
Повний текст джерелаRibosome biogenesis is an essential cellular process. Its alteration results in a strong activation of p53 and of other ribosome biogenesis surveillance pathways that remain to be identified. In vitro studies have shown that cancer cells display an enhanced sensitivity to ribosome biogenesis inhibition, indicating that targeting ribosome production would be a promising strategy for the development of new treatments. Conditional inactivation of the ribosome biogenesis factor Notchless (Nle) in the adult mouse intestine leads to the rapid elimination of intestinal stem cells and progenitors. During my thesis, I completed the study of this phenotype. I have shown that this elimination occurred in the absence of detectable alterations in protein synthesis, and that, while it was primarily mediated by p53, cell cycle arrest in the intestinal crypts was independent of p21. Moreover, to assess the impact of ribosome biogenesis alterations on intestinal tumorigenesis, I monitored the consequences of Nle loss-of-function on tumor initiation following Apc deletion. This study revealed that, though Nle loss-of-function attenuates proliferative compartment expansion, Apc deficiency improves stem cell and progenitor resistance to ribosome biogenesis defects. Our results thus alert on possible limitations of ribosome biogenesis inhibition-based therapeutic strategies in the context of colorectal cancer. More generally, this work hints towards complex interactions between the Wnt signaling pathway and the ribosome biogenesis pathway in vivo
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.
Повний текст джерелаRibosome 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
Castle, 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.
Повний текст джерелаBischoff, Lukas. "Structural analysis of membrane protein biogenesis and ribosome stalling by cryo-electron microscopy." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-182074.
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