Literatura académica sobre el tema "ARN – Détérioration"
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Tesis sobre el tema "ARN – Détérioration"
Cartalas, Jérémy. "Characterization of the RNA maturation-degradation machinery in plant mitochondria". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ003.
Texto completoMitochondria are the site of energy production in eukaryotic cells. Mitochondria have their own transcriptome. In order to generate a mature and efficient transcriptome, a whole range of RNases are required for RNA maturation and degradation. Among these, the MNU2 protein has been characterized as having a role in maturation. But it could also play a role in degradation. During my PhD, I showed that MNU2 could be a hub for a degradosome, interacting with mtPNPase and a polyA polymerase. I generated mnu2 mutants, and in order to characterize its function I adapted new generation sequencing methods and applied them in reverse genetics approaches. My research has shown a decisive role for MNU2 in the definition of 5' monoP ends. It has also shed light on a potential 5'-3' degradation pathway
Audebert, Léna. "Mécanismes de la dégradation des ARN dépendants ou indépendants de la déadénylation". Electronic Thesis or Diss., Sorbonne université, 2022. http://www.theses.fr/2022SORUS374.
Texto completoRNA degradation is a critical step in maintaining the proper balance required for gene expression and its regulation. In eukaryotes, RNA decay is thought to be controlled by the speed of poly-A tail shortening. Below a threshold, the presence of an oligo-A tail leads to decapping activation and rapid RNA degradation. However, progressive deadenylation is not required for a major fast RNA degradation pathway, the nonsense mediated mRNA decay (NMD), which occurs independently of the size of a poly-A tail. Based on large-scale poly-A tail length measurements and RNA half-life estimates, we hypothesize that a deadenylation-independent degradation model, similar to NMD, applies to other unstable RNAs. This model predicts that changes in the deadenylation speed should not impact the half-life of these RNAs. Poly-A tail shortening could be thus considered as a parallel event rather than a requirement for RNA degradation. We found that, as predicted by a deadenylation-independent model of RNA degradation, an unstable reporter RNA that is insensitive to NMD, is not stabilized by an inhibition of deadenylation, even if it is highly sensitive to the decapping activity. These results were obtained in a "degron" system for quick and specific depletion of the proteins, which allows a minimal global perturbation of the tested cells. In line with these functional results, we identified unstable RNAs as a population of RNA molecules associated with the poly-A binding protein and conclude that long poly-A tails are a natural feature of unstable RNAs. Our results are consistent with recent large-scale estimates of poly-A tails length and RNA stability and imply that molecular mechanisms involved in the initiation of RNA degradation in eukaryotes remain to be discovered
Gilbert, Agathe. "Impact of protein-protein interactions and phosphorylation on RNA decapping for nonsense mediated mRNA decay (NMD)". Electronic Thesis or Diss., Sorbonne université, 2022. http://www.theses.fr/2022SORUS386.
Texto completoIn yeast, mRNA degradation is mainly initiated through the cleavage of the pyrophosphate bond between the mRNA and the cap structure at its 5’-end. While this step is important for the decay of most mRNAs, it is particularly critical to initiate the degradation of unstable RNA, targets of the NMD machinery. This pathway allows degradation of transcripts that contain a premature termination codon and thus is entirely dependent on translation. First considered as conserved throughout eucaryotes due to high sequence similarity of its core factors – the Upf proteins -, the discovery of the Smg proteins in C. elegans (Page et al., 1999) and the description of the SURF/DECID mechanism depending on phosphorylation of Upf1 (Kashima et al., 2006) indicated a divergence of NMD mechanisms between organisms. However, recently our laboratory described two NMD complexes revolving around Upf1 – named Detector and Effector - and identified the protein kinase Hrr25 as a member of a Upf1-decapping complex (Dehecq et al., 2018). The conserved protein kinase Hrr25 is the yeast equivalent of mammalian casein kinase 1 (CK1delta and CK1epsilon) and is involved in major cellular processes, including tRNA modification, ribosome biogenesis, transcription elongation and meiosis (Abdel-Fattah et al., 2015; Ghalei et al., 2015; Ye et al., 2016; Nemec et al., 2019). I demonstrated that the Hrr25 kinase activity has a role in NMD that is independent of its function in mRNA translation and DNA transcription. The association of Hrr25 to Upf1 was dependent on the kinase activity of the protein and on the presence of the decapping enzyme Dcp2. We identified conserved serine residues located in the C-terminal region of yeast Upf1 whose phosphorylation was dependent on Hrr25 and was modulated, like the phosphorylation of Upf1 in other organisms, by the presence of other NMD factors, such as Upf2 and Ebs1 (SMG5/7 equivalent). These results indicate that protein kinases can modulate NMD by direct interactions with the enzymes involved in RNA degradation and suggest that, contrary to previous beliefs, protein kinases are universally required for NMD
Chamois, Sébastien. "Etude de la dégradation des ARN messagers aberrants par la voie de surveillance du No-Go Decay chez Saccharomyces cerevisiae". Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS023.pdf.
Texto completoGene expression is a complex mechanism that can lead to the production of aberrant messenger RNA that may in turn disrupt cell homeostasis. In eukaryotes, it exists several surveillance pathways in charge of degrading such RNA in the cytoplasm. The No-Go Decay (NGD) is one of those and degrades mRNA containing stacks of stalled ribosomes. This mechanism is characterized by an endoribonuclease that initiates cleavages upstream of the stall sequence. Their precise location, still under debate in the literature, has proven crucial in the understanding of the exact role of the NGD in the cytoplasm. During my thesis, we studied this surveillance pathway, using mRNAs expressing a 3′-ribozyme to produce truncated transcripts in vivo to mimic naturally occurring truncated mRNAs known to trigger NGD. Thanks to this technique, we were able to show that a unique endonucleolytic cleavage, which we find to be Hel2 and Cue2-dependent, occurs eight nucleotides upstream of the first P-site nucleotide within the third stacked ribosome. We demonstrate that this event produces a 3’-NGD RNA, which has a hydroxylated 5’-extremity that is then 5’-phosphorylated by the Trl1 kinase. Ultimately, we suggest that 5’-3’ degradation pathway is then involved in the degradation of this RNA with the action of Xrn1 and Dxo1
Dehecq, Marine. "Composition et dynamique des complexes protéiques impliqués dans le "nonsense-mediated mRNA decay" chez la levure Saccharomyces cerevisiae". Electronic Thesis or Diss., Sorbonne université, 2018. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2018SORUS538.pdf.
Texto completoNonsense-Mediated mRNA Decay (NMD) detects and degrades RNA for which translation ends prematurely. It affects a large diversity of cytoplasmics RNAs; it is the major decay pathway for aberrants RNAs.In yeast, NMD targeted RNAs have a short open reading frame and a long 3’-UTR. How these two features lead to an efficient degradation through NMD and what are the steps of this mechanism is still unclear.From 112 affinity purifications of NMD factors followed by an analysis using quantitative mass spectrometry, we identified two distinct complexes. Those complexes were mutually exclusive and both contained Upf1, the major NMD protein. A first complex, named Detector, might have a role in the NMD substrates recognition whereas the second one, named Effector, would initiate the degradation through a direct interaction with the decapping machinery.The factors involved in our new model are all conserved throughout eukaryotes and the steps we describe have potential equivalents in other species. Our data suggest a new paradigm for the NMD mechanism that would be organised around a shared universal base to which specific steps could be added in certain organisms or for certain types of RNA substrates
Yeramala, Lahari. "Caractérisation de complexes responsables de la dégradation des ARNm non-sens". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV008/document.
Texto completoNonsense-mediated mRNA decay (NMD) is an important eukaryotic quality control mechanism that recognizes and degrades mRNA containing a premature termination codon (PTC). Up-frameshift proteins constitute the conserved core NMD factors (UPF1, UPF2 and UPF3). They mediate the recognition of a NMD substrate, i.e. a ribosome stalled at a PTC. UPF proteins were shown to associate with eukaryotic release factors (eRF1 and eRF3) and were suggested to impede translation termination. We showed that, at a normal termination codon, Poly(A)-binding protein (PABP) stimulates translation termination by directly interacting with eRF3a. Using a reconstituted in vitro translation system, we studied translation termination in the presence of the factors PABP and UPF1 using biochemistry and single particle electron cryo-microscopy (Cryo-EM). Additionally, we analysed the role of the other NMD factors UPF2 and UPF3B in translation termination in vitro. We discovered a novel role for UPF3B in translation termination. Moreover, we observed a novel interaction between UPF3B and the SMG1-8-9 kinase complex. The presence of UPF3B affects the kinase activity of SMG1 and thus the phosphorylation state of UPF1. Our results highlight a much more complex interplay of the NMD factors with the translation termination machinery and SMG1 kinase than anticipated
Esquerre, Thomas. "Rôle des régulations de la stabilité des ARN messagers dans l'adaptation d'Escherichia coli à son environnement". Thesis, Toulouse, INSA, 2014. http://www.theses.fr/2014ISAT0016/document.
Texto completoBacterial adaptation to environment results from regulations of gene expression to optimize cell physiology to growth conditions. Control of mRNA concentration is one of those regulations. It depends on both variations of transcription and transcript degradation. Although these two mechanisms are well defined at the molecular level in E. coli, their respective impact on mRNA level regulation is still unknown at the genome scale because of a lack of omic data on mRNA stability during changing environment. Moreover, parameters determining messenger stability are not yet clearly identified and have never been ranked.During this PhD, the stability of each of the E. coli mRNAs was measured through stabilome determination. More precisely, the half-life of around 70 % of all messengers was reliably determined at four different growth rates obtained in the same growth conditions in chemostats. For the first time, this study demonstrated that increase of growth rate led to global increase of transcript degradation. Integration of these data with transcriptomic data showed that although transcription was the main mechanism which regulated mRNA level, messenger degradation exerted an opposite effect in most of the cases. The role of messenger degradation in the control of mRNA concentration was significantly accentuated with increasing growth rate and affected particularly genes involved in central carbon metabolism. Using mRNA stability data produced at different growth rates, integrative biology approaches allowed identification and ranking of the determinants of messenger stability. mRNA concentration which was the main parameter, but also codon bias, length of the coding sequence, sequence motifs contributed to transcript stability. However, although the hierarchy of determinants remained identical with variations of growth rate, the stability of mRNAs belonging to specific functional categories differed with the growth rate. Nevertheless, other determinants of messenger half-life, in particular at high growth rates still remain to be discovered. The CsrA protein, which belongs to the Csr system, is one example of a post-transcriptional regulator. CsrA positively or negatively controls expression of several mRNAs by mechanisms able to modify transcript stability. Nevertheless, the extent of CsrA effect on mRNA stability at the omic level has never been studied. By comparing stabilomes and transcriptomes of the wild type strain with a strain with reduced CsrA activity, the indirect transcriptional effects of CsrA were measured and new mRNAs whose stability was targeted by CsrA (mostly stabilized), were identified. Moreover, the CsrD protein, a regulator of CsrB/C small RNA stability, was not involved in mRNA stability regulation, but played a role in transcriptional regulation of many genes independently of its role in the Csr system. To conclude, this work provides a better understanding of the regulation of the mRNA stability. It identifies mRNA stability determinants and characterizes the role and extent of mRNA stability regulation in the control of messenger concentration. The study underlines the importance of this regulation in the process of bacterial adaptation
Fourati-Kammoun, Zeineb. "Etude structurale et fonctionnelle de protéines impliquées dans la dégradation des ARNm aberrants". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114826.
Texto completoMRNA translation process is finely tuned thanks to the regulatory mechanisms evolved by the cell controlling its rate, efficiency and fidelity. Indeed, mRNAs are often subjected to transcription and maturation errors. In particular, mRNA harboring premature stop codons (PTC) in their open reading frames could be translated into truncated proteins with a deleterious impact on the cell. Thus, such mRNAs are rarely detected in the cell as they are rapidly degraded thanks to the NMD (Nonsence mediated mRNA Decay) pathway. In yeast Saccharomyces cerevisiae, this process is governed by the Upf1, Upf2 and Upf3 proteins forming the “surveillance complex”, the termination factors (eRF1 and eRF3) as well as some other poorly characterized factors like Ebs1 protein. In addition, degradation of such mRNAs is enhanced by rapid degradation of the 5’ cap or decapping. In this work, we focused on the characterization of some proteins involved in this process. In particular, we addressed the structural characterization of Upf2 protein, the central component of the surveillance complex. In addition, we characterized a functional domain of Pat1 protein, a strong decapping enhancer. This study allowed us to give a new insight into the role of these proteins in mRNA quality control and decay
Colotte, Marthe. "Stabilité chimique et conformationnelle de l’ADN à l’état sec et à température ambiante". Bordeaux 2, 2008. http://www.theses.fr/2008BOR21535.
Texto completoSchmitt, Thomas. "Mécanismes de dégradation de revêtements base CrN élaborés par arc-PVD : Intérêt d'une nano-architecture". Phd thesis, Ecole Centrale de Lyon, 2010. http://tel.archives-ouvertes.fr/tel-00633784.
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