m 6 A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation
Top Cited Papers
- 27 February 2015
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 347 (6225), 1002-1006
- https://doi.org/10.1126/science.1261417
Abstract
Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N6-methyladenosine (m6A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m6A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m6A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner.Keywords
Funding Information
- Flight Attendant Medical Research Institute
- Israel Science Foundation (1667/12, 41/11, 1796/12)
- Israeli Centers of Excellence (I-CORE) Program
- Ernest and Bonnie Beutler Research Program
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