GC content shapes mRNA decay and storage in human cells
2019
Courel, Maïte | Clément, Yves | Foretek, Dominika | Vidal Cruchez, Olivia | Yi, Zhou | Benassy, Marie-Noëlle | Kress, Michel | Vindry, Caroline | Bénard, Marianne | Bossevain, Clémentine | Antoniewski, Christophe | Morillon, Antonin | Brest, Patrick | Hubstenberger, Arnaud | Crollius, Hugues, Roest | Standart, Nancy | Weil, Dominique | Institut Jacques Monod (IJM (UMR_7592)) ; Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS) | Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP) ; Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro) | Bioinformatique [IBPS] (IBPS-Artbio) ; Institut de Biologie Paris Seine (IBPS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Control of protein expression results from the fine tuning of mRNA synthesis, decay and translation. These processes, which are controlled by a large number of RNA-binding proteins and by localization in RNP granules such as P-bodies, appear often intimately linked although the rules of this interplay are not well understood. In this study, we combined our recent P-body transcriptome with various transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors. This analysis revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA decay. It also rationalized why PBs mRNAs have a strikingly low protein yield. We report too the existence of distinct mRNA decay pathways with preference for AU-rich or GC-rich transcripts. Compared to this impact of the GC content, sequence-specific RBPs and miRNAs appeared to have only modest additional effects on their bulk targets. Altogether, these results lead to an integrated view of post-transcriptional control in human cells where most regulation at the level of translation is dedicated to AU-rich mRNAs, which have a limiting protein yield, whereas regulation at the level of 5' decay applies to GC-rich mRNAs, whose translation is optimal.
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تم تزويد هذا السجل من قبل Institut national de la recherche agronomique