The N⁶-methyladenosine demethylase ALKBH5 negatively regulates the osteogenic differentiation of mesenchymal stem cells through PRMT6.

ABSTRACT: N⁶-methyladenosine (m⁶A) modification is widespread in messenger RNAs and increasing evidence suggests the crucial roles of m⁶A in cell differentiation and tissue development. However, whether m⁶A modulates the osteogenic differentiation of mesenchymal stem cells (MSCs) has not been fully elucidated. Here we show that conditional knockout of the demethylase Alkbh5 in bone marrow MSCs strengthened bone mass in mice. Loss- and gain-of-function studies demonstrated that ALKBH5 negatively regulates the osteogenic differentiation of MSCs in vitro. At a mechanistic level, meRIP-seq and RNA-seq in MSCs following knockdown of ALKBH5 revealed changes in transcripts of PRMT6 containing consensus m⁶A motifs required for demethylation by ALKBH5. F

SUBMITTER: Li Z 

PROVIDER: S-EPMC8178363 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature