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

Mehravar, M.; Kumar, Y.; Olshansky, M.; Bansal, D.; Dent, C.; Hathiwala, D.; Zhang, Z.; Gandhi, H.; Fulcher, A.; Huang, C.; Price, J.; Arumugam, S.; Ceman, S.; Balasubramanian, S.; Papas, B. N.; Morgan, M.; Miska, E. A.; Schittenhelm, R. B.; Tripathi, P.; Das, P. P.

doi:10.1101/2021.08.11.456030

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bioRxiv · 10.1101/2021.08.11.456030

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

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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 -- 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 the m6A pathway. 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-3{beta} mRNA through m6A that stabilises the {beta}-CATENIN expression of a WNT/{beta}-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 m6A-reader, MOV10 mediates mRNA decay via m6A that impact embryonic stem cell biology.

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Mehravar, M., Kumar, Y., Olshansky, M., Bansal, D., Dent, C., Hathiwala, D., Zhang, Z., Gandhi, H., Fulcher, A., Huang, C., Price, J., Arumugam, S., Ceman, S., Balasubramanian, S., Papas, B. N., Morgan, M., Miska, E. A., Schittenhelm, R. B., Tripathi, P., Das, P. P.. 2021-08-12. MOV10 facilitates messenger RNA decay in an N6-methyladenosine (m6A) dependent manner to maintain the mouse embryonic stem cells state. https://doi.org/10.1101/2021.08.11.456030

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