ALKBH5-mediated m⁶A mRNA methylation governs human embryonic stem cell cardiac commitment.

ABSTRACT: N6-methyladenosine (m⁶A), as the most abundant modification of mammalian messenger RNAs, is essential for tissue development and pathogenesis. However, the biological significance of m⁶A methylation in cardiac differentiation and development remains largely unknown. Here, we identify that the downregulation of m⁶A demethylase ALKBH5 is responsible for the increase of m⁶A methylation and cardiomyocyte fate determination of human embryonic stem cells (hESCs) from mesoderm cells (MESs). In contrast, ALKBH5 overexpression remarkably blocks cardiomyocyte differentiation of hESCs. Mechanistically, KDM5B and RBBP5, the components of H3K4 modifying enzyme complexes, are identified as downstream targets for ALKBH5 in cardiac-committed hESCs. Loss of funct

SUBMITTER: Han Z 

PROVIDER: S-EPMC8408434 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature