MOV10 facilitates messenger RNA decay in an N6-methyladenosine (m6A) dependent manner to maintain the mouse embryonic stem cells state

Abstract N6 -methyladenosine (m 6 A) is the most predominant internal mRNA modification in eukaryotes, recognised by its reader proteins (so-called m 6 A-readers) for regulating subsequent mRNA fates — splicing, export, localisation, decay, stability, and translation — to control several biological processes. Although a few m 6 A-readers have been identified, yet the list is incomplete. Here, we identify a new m 6 A-reader protein, Moloney leukaemia virus 10 homologue (MOV10), in the m 6 A pathway. MOV10 recognises m 6 A-containing mRNAs with a conserved GGm 6 ACU motif. Mechanistic studies uncover that MOV10 facilitates mRNA decay of its bound m 6 A-containing mRNAs in an m 6 A-dependent manner within the cytoplasmic processing bodies (P-bodies). Furthermore, MOV10 decays the Gsk-3ß mRNA through m 6 A that stabilises the ß-CATENIN expression of a WNT/ß-CATENIN signalling pathway to regulate downstream NANOG expression for maintaining the mouse embryonic stem cells (mESCs) state. Thus, our findings reveal how a newly identified m 6 A-reader, MOV10 mediates mRNA decay via m 6 A that impact embryonic stem cell biology.