N⁶-Methyladenosine Guides mRNA Alternative Translation during Integrated Stress Response.

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 N⁶-methyladenosine (m⁶A). While depleting m⁶A demethylases represses ATF4 reinitiation, knocking down m⁶A methyltransferases promotes ATF4 translation. We demonstrate that m⁶A in the 5' UTR controls ribosome scanni

SUBMITTER: Zhou J 

PROVIDER: S-EPMC5816726 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature