Global ETD Search

1	Study of the interactome of UPF1, a key factor of Nonsense-mediated decay in Arabidopsis thaliana / Etude de l’interactome de UPF1, un acteur central du nonsense-mediated decay chez Arabidopsis thaliana Chicois, Clara 31 January 2018 (has links) L’ARN hélicase UPF1 est un facteur clé du Nonsense-Mediated Decay (NMD), un mécanisme impliqué dans le contrôle de la qualité des ARNm et la régulation de l’expression des gènes. Malgré d’importantes fonctions chez les plantes, le NMD y est peu décrit. Cette thèse présente l’identification et l’étude des protéines interagissant avec UPF1 chez Arabidopsis. Nous avons identifié un nouveau réseau d’interaction protéine-protéine entre UPF1 et des répresseurs de traduction dans les P-bodies. Nous proposons un modèle dans lequel la répression traductionnelle exerce une action protectrice sur les cibles du NMD. Notre approche a également identifié de nouveaux composants des P-bodies, comme l’endonucléase UCN. Son étude détaillée a révélé un lien direct avec la machinerie de decapping ainsi que de possibles rôles dans la signalisation hormonale ou les mécanismes de défense, suggérant que la modulation de l’expression d’UCN pourrait influencer d’importantes caractéristiques agronomiques. Ce travail décrit des facteurs associés à UPF1 jusqu’alors inconnus, leur étude permettra de découvrir de nouveaux mécanismes impliqués dans l’équilibre entre la traduction, le stockage et la dégradation des ARNm chez les plantes. / The RNA helicase UPF1 is a key factor of Nonsense-Mediated Decay (NMD), a paneukaryotic mechanism involved in mRNA quality control and fine-tuning of gene expression. Despite important biological functions in plants, NMD is poorly described compared to other eukaryotes. This thesis presents the identification and study of UPF1 interacting proteins in Arabidopsis. Using approaches based on immunoaffinity and mass spectrometry, we identified a novel protein-protein interaction network between UPF1 and translation repressors in P-bodies. We propose a model in which translation repression exerts a protective action on NMD targets in plants. Our approach also identified novel P-body components, including the UCN endonuclease. A detailed study revealed its direct link with the decapping machinery and possible roles in hormone signaling and defense mechanisms, suggesting that the modulation of UCN expression could influence important agronomical traits. This work describes hitherto unknown UPF1 associated factors, their study will provide novel insights into the mechanisms involved in the balance between mRNA translation, storage and decay in plants. NMD UPF1 Répression traductionnelle Arabidopsis thaliana NMD UPF1 Translation repression Arabidopsis thaliana 572.8 581
2	Processing Body Formation Limits Proinflammatory Cytokine Synthesis in Endotoxin-Tolerant Monocytes and Murine Septic Macrophages McClure, Clara, Brudecki, Laura, Yao, Zhi Q., McCall, Charles E., El Gazzar, Mohamed 16 October 2015 (has links) An anti-inflammatory phenotype with pronounced immunosuppression develops during sepsis, during which time neutrophils and monocytes/macrophages limit their Toll-like receptor 4 responses to bacterial lipopolysaccharide (LPS/endotoxin). We previously reported that during this endotoxin-tolerant state, distinct signaling pathways differentially repress transcription and translation of proinflammatory cytokines such as TNFα and IL-6. Sustained endotoxin tolerance contributes to sepsis mortality. While transcription repression requires chromatin modifications, a translational repressor complex of Argonaute 2 (Ago2) and RNA-binding motif protein 4 (RBM4), which bind the 3′-UTR of TNFα and IL-6 mRNA, limits protein synthesis. Here, we show that Dcp1 supports the assembly of the Ago2 and RBM4 repressor complex into cytoplasmic processing bodies (p-bodies) in endotoxin-tolerant THP-1 human monocytes following stimulation with LPS, resulting in translational repression and limiting protein synthesis. Importantly, this translocation process is reversed by Dcp1 knockdown, which restores TNFα and IL-6 protein levels. We also find this translational repression mechanism in primary macrophages of septic mice. Because p-body formation is a critical step in mRNA translation repression, we conclude that Dcp1 is a major component of the translational repression machinery of endotoxin tolerance and may contribute to sepsis outcome. Dcp1 endotoxin tolerance microRNA sepsis severe systemic inflammation toll-like receptor signaling translation repression Internal Medicine
3	Structural and functional characterisation of the CCR4- NOT deadenylation complex / Caractérisation fonctionnelle et structurale du complexe de déadénylation CCR4-NOT Roudko, Vladimir 19 September 2014 (has links) La dégradation des ARN messagers (ARNm) est un processus universel extrêmement complexe. D’une manière semblable aux polymerases pour la transcription et ribosomes pour la traduction, les complexes de protéines effectuant la dégradation des ARNm sont précisément régulés. La dégradation des ARNm eucaryotes s’effectue selon un schéma conservé évolutivement qui est initié par la déadénylation résultant dans la formation de transcrits avec des queues polyA courtes. De tels intermédiaires sont alors dégradés par le clivage de leur coiffe suivi par une digestion exonucléolytique 5’-3’ effectuée par Xrn1, ou alternativement par une digestion 3 ’-5’ catalysée par l’exosome. Dans ma thèse je présente une dissection fonctionnelle du complexe de déadénylation CCR4-NOT basée sur son analyse structurale. Je me suis essentiellement intéressé à cinq questions fondamentales concernant ce complexe : La formation du complexe CCR4-NOT complexe est-elle requise pour la déadénylation ? Quel est le rôle moléculaire de sous-unités Not2/3/5 du complexe ? Pourquoi la protéine Not1 est-elle essentielle chez la levure ? Le complexe CCR4-NOT joue-t-il un rôle dans la répression de la traduction ? Comment le complexe CCR4-NOT est-il ciblé sur ses substrats ARNm ? / MRNA degradation is a highly complex and versatile process. In a manner similar to polymerase complexes in transcription and ribosomes in translation, protein complexes mediating mRNA decay are tightly regulated. Eukaryotic mRNA decay follows a conserved pathway initiated by deadenylation that generates transcripts with short polyA tails. The latter intermediates are degraded either by decapping followed with 5’-3’ trimming mediated by Xrn1, or by exosome-mediated digestion in the 3’-5’ direction. In my thesis I present a functional dissection of the Ccr4-Not deadenylase complex based on its structural analysis. Essentially, I addressed five fundamental questions related to this complex: Is CCR4-NOT complex formation required for deadenylation activity? What is the molecular role of associated Not2/3/5 subunits? Why is the Not1 protein essential in yeast? Does the CCR4-NOT complex play role in translation regulation? How is the CCR4-NOT complex targeted to its mRNA substrates? CCR4-NOT Déadénylation Répression de la traduction Analyse structurale et fonctionelle CCR4-NOT Deadenylation Translation repression Structural and functional analysis 571.4 572.8
4	Translační iniciační faktory proteinové rodiny 4E a jejich vliv na regulaci genové exprese / 4E translation initiation factors and their influence on regulation of gene expression Lettrich, Patrik January 2021 (has links) The translation represents one of the most crucial processes in the cell. That is why it is often targeted by various regulations. Its initiation phase has a particularly important role in regulatory processes. Initiation of translation usually starts by recognition and binding of canonical eukaryotic initiation factor 4E1 (eIF4E1) to the methylguanosine cap present on the 5' end of the majority of eukaryotic mRNA. The family of 4E translation initiation factors contains two more members - eIF4E2 and eIF4E3. Those two proteins can bind cap structure as well which predetermines it to function in the regulation of translation. Protein eIF4E2 is well known for being a translational repressor in development processes and it takes part in specific miRNA-dependent silencing. It was proven to be able to initiate translation in hypoxia which is consistent with its proposed role in hypoxic tumor cells. The biological roles of the protein eIF4E3 are much less understood. This thesis propounds the picture of the overall functions of all discussed translation initiation factors using cell lines with their overexpression or deletion. Experimental data confirmed the role of the eIF4E2 in the regulation of developmental processes. Cell lines with deleted eIF4E2 and eIF4E3 were characterized based on the influence...
5	Stage-specific germ cell marker genes function in establishment and germ cell lineage commitment of pluripotent stem cells / Stadien-spezifische Keimzellmarker-Gene wirken in der Etablierung von pluripotenten Stammzellen und leisten einen Beitrag zu deren Herkunft Xu, Xingbo 19 October 2012 (has links) No description available. 500 Naturwissenschaften WA000 Biology (incl. Psychology) Stammzellen Keimzellen ESCs Pluripotenz iPSCs Dppa3 Dnmt3a Gtl2 IG-DMR Dlk1-Dio3 Imprinting Vitamin C Dazl Spleißvariante translationale Repression RNA-Bindung Stem cells germ cells ESCs pluripotency iPSCs Dppa3 Dnmt3a Gtl2 IG-DMR Dlk1-Dio3 imprinting Vitamin C. Dazl splice variant translation repression RNA binding 42

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