Datasets

Title	N6-Methyladenosine Guides mRNA Alternative Translation during Integrated Stress Response
Organism
Number of Samples	10
Release Date	2017/08/14 00:00
Sequencing Types
Protocol Details

Title
Authors	Zhou J,Wan J,Shu XE,Mao Y,Liu XM,Yuan X,Zhang X,Hess ME,Brüning JC,Qian SB
Journal	Molecular cell
Publication Date	2018 Feb 15
Abstract	The integrated stress response (ISR) facilitates cellular adaptation to stress conditions via the common target eIF2α. During ISR, the selective translation of stress-related mRNAs often relies on alternative mechanisms, such as leaky scanning or reinitiation, but the underlying mechanism remains incompletely understood. Here we report that, in response to amino acid starvation, the reinitiation of ATF4 is not only governed by the eIF2α signaling pathway, but is also subjected to regulation by mRNA methylation in the form of N 6 -methyladenosine (m 6 A). While depleting m 6 A demethylases represses ATF4 reinitiation, knocking down m 6 A methyltransferases promotes ATF4 translation. We demonstrate that m 6 A in the 5' UTR controls ribosome scanning and subsequent start codon selection. Global profiling of initiating ribosomes reveals widespread alternative translation events influenced by dynamic mRNA methylation. Consistently, Fto transgenic mice manifest enhanced ATF4 expression, highlighting the critical role of m 6 A in translational regulation of ISR at cellular and organismal levels. Copyright © 2018 Elsevier Inc. All rights reserved.
PMC	PMC5816726
PMID	29429926
DOI

Zhou et al. 2017 (PRJNA398285)