N⁶-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications.

ABSTRACT: Internal N⁶-methyladenosine (m⁶A) modification is widespread in messenger RNAs (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) and Mettl14. To understand the role of m⁶A in development, we deleted Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displayed markedly decreased proliferation and premature differentiation, suggesting that m⁶A modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis. Mechanistically, we discovered a genome-wide increase in specific histone modifications in Mettl14 knockout versus control NSCs. These changes correlated with altered gene expression

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6317335 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature