GC content shapes mRNA storage and decay in human cells

Maïté Courel (1) , Yves Clément (2) , Clémentine Bossevain (1) , Dominika Foretek (3) , Olivia Vidal Cruchez (4) , Zhou Yi (5) , Marianne Bénard (1) , Marie-Noëlle Benassy (1) , Michel Kress (1) , Caroline Vindry (6) , Michèle Ernoult-Lange (1) , Christophe Antoniewski (1) , Antonin Morillon (3) , Patrick Brest (4) , Arnaud Hubstenberger (5) , Hugues Roest Crollius (2) , Nancy Standart (6) , Dominique Weil (1)

1 IBPS - Institut de Biologie Paris Seine
2 IBENS - Institut de biologie de l'ENS Paris
3 DIG CANCER - Dynamique de l'information génétique : bases fondamentales et cancer
4 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
5 IBV - Institut de Biologie Valrose
6 Department of Biochemistry, University of Cambridge

mRNA translation and decay appear often intimately linked although the rules of this interplay are poorly understood. In this study, we combined our recent P-body transcriptome with transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors, and with available CLIP and related data. This revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA stability: P-bodies contain mostly AU-rich mRNAs, which have a particular codon usage associated with a low protein yield; AU-rich and GC-rich transcripts tend to follow distinct decay pathways; and the targets of sequencespecific RBPs and miRNAs are also biased in terms of GC content. Altogether, these results suggest an integrated view of post-transcriptional control in human cells where most translation regulation is dedicated to inefficiently translated AU-rich mRNAs, whereas control at the level of 5' decay applies to optimally translated GC-rich mRNAs.

Keywords: mRNA decay; mRNA storage; post-transcriptional regulation.; GC content; P-bodies; chromosomes; codon usage; gene expression; human

Domains: Life Sciences [q-bio]

Maïté Courel, Yves Clément, Clémentine Bossevain, Dominika Foretek, Olivia Vidal Cruchez, et al.. GC content shapes mRNA storage and decay in human cells. eLife, 2019, 8, pp.e49708. ⟨10.7554/elife.49708⟩. ⟨hal-03457618⟩