GC content shapes mRNA storage and decay in human cells
- Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, France
- Ecole Normale Supérieure, France
- Institut Curie, France
- Université Côte d'Azur, CNRS, INSERM, France
- University of Cambridge, United Kingdom
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.
Data availability
RNA-Seq gene data have been deposited in SRA under accession codes E-MTAB-4091 for the polysome profiling after DDX6 silencing, E-MTAB-5577 for the transcriptome after PAT1B silencing, and E-MTAB-5477 for the PB transcriptome, all in HEK293 cells.RNA-Seq gene data have been deposited in GEO under accession codes GSE115471 and GSE114605 for the transcriptome after XRN1 silencing in HeLa and HCT116 cells, respectively.ENCODE datasets are available at https://www.encodeproject.org under accession codes ENCSR893EFU for the DDX6 eClip experiment, and ENCSR109IQO for the transcriptome after DDX6 silencing in K562 cells.All data generated or analyzed during this study are included in the Supplementary file 1.
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RNA-Seq of purified P-bodies from HEK293 cellsArrayExpress, E-MTAB-5477.
Article and author information
Author details
Christophe Antoniewski
Hugues Roest Crollius
Funding
Association pour la Recherche sur le Cancer (Subvention Fixe)
- Dominique Weil
Agence Nationale de la Recherche (ANR-14-CE09-0013-01)
- Dominique Weil
European Research Council (DARK consolidator grant)
- Antonin Morillon
Agence Nationale de la Recherche (ANR-11-LABX-0028-01)
- Antonin Morillon
Canceropole PACA
- Patrick Brest
Biotechnology and Biological Sciences Research Council
- Nancy Standart
Newton Trust and Foundation Wiener
- Nancy Standart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Karsten Weis, ETH Zurich, Switzerland
Version history
- Received: June 26, 2019
- Accepted: December 18, 2019
- Accepted Manuscript published: December 19, 2019 (version 1)
- Version of Record published: January 6, 2020 (version 2)
Copyright
© 2019, Courel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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GC content shapes mRNA storage and decay in human cells
eLife 8:e49708.
https://doi.org/10.7554/eLife.49708
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