GC content shapes mRNA storage and decay in human cells
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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.
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Funder: Canceropôle PACA; FundRef: http://dx.doi.org/10.13039/501100006331
Funder: Biotechnology and Biological Sciences Research Council; FundRef: http://dx.doi.org/10.13039/501100000268
Funder: Isaac Newton Trust; FundRef: http://dx.doi.org/10.13039/501100004815
Funder: Fondation Philippe Wiener - Maurice Anspach; FundRef: http://dx.doi.org/10.13039/501100003138
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Agence Nationale de la Recherche (ANR-14-CE09-0013-01)
European Research Council (DARK consolidator grant)
Agence Nationale de la Recherche (ANR-11-LABX-0028-01)