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Elife. 2019 Dec 19;8. pii: e49708. doi: 10.7554/eLife.49708.

GC content shapes mRNA storage and decay in human cells.

Author information

1
Sorbonne Université, CNRS, Institut de Biologie Paris Seine (IBPS), Laboratoire de Biologie du Développement, Paris, France.
2
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Paris, France.
3
ncRNA, Epigenetic and Genome Fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Sorbonne Université, Paris, France.
4
Université Côte d'Azur, CNRS, INSERM, IRCAN, FHU-OncoAge, Nice, France.
5
Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France.
6
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
7
Sorbonne Université, CNRS, Institut de Biologie Paris Seine (IBPS), ARTbio Bioinformatics Analysis Facility, Paris, France.

Abstract

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 sequence-specific 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:

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

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