TY - JOUR T1 - GC content shapes mRNA decay and storage in human cells JF - bioRxiv DO - 10.1101/373498 SP - 373498 AU - Maïté Courel AU - Yves Clément AU - Dominika Foretek AU - Olivia Vidal Cruchez AU - Zhou Yi AU - Marie-Noëlle Benassy AU - Michel Kress AU - Caroline Vindry AU - Marianne Bénard AU - Clémentine Bossevain AU - Christophe Antoniewski AU - Antonin Morillon AU - Patrick Brest AU - Arnaud Hubstenberger AU - Hugues Roest Crollius AU - Nancy Standart AU - Dominique Weil Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/25/373498.abstract N2 - 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. ER -