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Etude de la dégradation des ARN messagers aberrants par la voie de surveillance du No-Go Decay chez Saccharomyces cerevisiae

Abstract : Gene 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.
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Submitted on : Sunday, September 26, 2021 - 1:02:26 AM
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  • HAL Id : tel-03354717, version 1

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Sébastien Chamois. Etude de la dégradation des ARN messagers aberrants par la voie de surveillance du No-Go Decay chez Saccharomyces cerevisiae. Biochimie, Biologie Moléculaire. Sorbonne Université, 2020. Français. ⟨NNT : 2020SORUS023⟩. ⟨tel-03354717⟩

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