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Composition et dynamique des complexes protéiques impliqués dans le "nonsense-mediated mRNA decay" chez la levure Saccharomyces cerevisiae

Abstract : Nonsense-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.
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Marine Dehecq. Composition et dynamique des complexes protéiques impliqués dans le "nonsense-mediated mRNA decay" chez la levure Saccharomyces cerevisiae. Biochimie, Biologie Moléculaire. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS538⟩. ⟨tel-02489767⟩

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