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

Abstract

N6-methyladenosine (m6A) is the most predominant internal mRNA modification in eukaryotes, recognised by its reader proteins (so-called m6A-readers) for regulating subsequent mRNA fates, such as splicing, export, localisation, decay, stability, and translation to control several biological processes. Although a few m6A-readers have been identified, yet the list is incomplete. Here, we identify a new m6A-reader protein, Moloney leukaemia virus 10 homologue (MOV10), in mouse embryonic stem cells (mESCs). MOV10 recognises m6A-containing mRNAs with a conserved GGm6ACU motif. Mechanistic studies uncover that MOV10 facilitates mRNA decay of its bound m6A- containing mRNAs in an m6A-dependent manner within the cytoplasmic processing bodies (P-bodies). Furthermore, MOV10 decays the Gsk-3beta mRNA through m6A that stabilises the BETA-CATENIN expression of a WNT/BETA-CATENIN signalling pathway to regulate downstream NANOG expression for maintaining the mESC state. Thus, our findings reveal how a newly identified m6A-reader, MOV10 mediates mRNA decay via m6A that impact embryonic stem cell biology.

ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition

“…We now demonstrate that tagged or endogenous ZCCHC3 and MOV10 co-IP from 293T cells, an association that is dependent upon RNA ( Fig 6A and 6B ). Two other studies also identified MOV10 as an interacting partner of ZCCHC3 by quantitative MS [ 65 , 66 ]. Similarly, FLAG-tagged ZCCHC3 co-IPs with endogenous ZAP ( Fig 6C ), and FLAG-tagged ZAP co-IPs with V5-TEV-ZCCHC3, in each case independently of RNA ( Fig 6D ).…”