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Pré-Publication, Document De Travail Année : 2019

GC content shapes mRNA decay and storage in human cells

Maïte Courel
Dominika Foretek
  • Fonction : Auteur
Olivia Vidal Cruchez
  • Fonction : Auteur
Zhou Yi
  • Fonction : Auteur
Marie-Noëlle Benassy
  • Fonction : Auteur
Michel Kress
  • Fonction : Auteur
Caroline Vindry
  • Fonction : Auteur
Marianne Bénard
  • Fonction : Auteur
Clémentine Bossevain
  • Fonction : Auteur
Christophe Antoniewski
Antonin Morillon
Patrick Brest
Arnaud Hubstenberger
  • Fonction : Auteur
Hugues Roest Crollius
  • Fonction : Auteur
Nancy Standart
Dominique Weil

Résumé

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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Dates et versions

hal-02415568 , version 1 (17-12-2019)

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Maïte Courel, Yves Clément, Dominika Foretek, Olivia Vidal Cruchez, Zhou Yi, et al.. GC content shapes mRNA decay and storage in human cells. 2019. ⟨hal-02415568⟩
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