M⁶A-independent genome-wide METTL3 and METTL14 redistribution drives the senescence-associated secretory phenotype.

ABSTRACT: Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex that catalyses messenger RNA N⁶-methyladenosine (m⁶A) modification. Despite the expanding list of m⁶A-dependent functions of the methyltransferase complex, the m⁶A-independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 transcriptionally drives the senescence-associated secretory phenotype (SASP) in an m⁶A-independent manner. METTL14 is redistributed to the enhancers, whereas METTL3 is localized to the pre-existing NF-κB sites within the promoters of SASP genes during senescence. METTL3 and METTL14 are necessary for SASP. However, SASP is not r

SUBMITTER: Liu P 

PROVIDER: S-EPMC8035315 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature