| Literature DB >> 25569111 |
Shay Geula1, Sharon Moshitch-Moshkovitz2, Dan Dominissini3, Abed AlFatah Mansour1, Nitzan Kol2, Mali Salmon-Divon2, Vera Hershkovitz2, Eyal Peer2, Nofar Mor1, Yair S Manor1, Moshe Shay Ben-Haim2, Eran Eyal2, Sharon Yunger2, Yishay Pinto4, Diego Adhemar Jaitin5, Sergey Viukov1, Yoach Rais1, Vladislav Krupalnik1, Elad Chomsky1, Mirie Zerbib1, Itay Maza1, Yoav Rechavi1, Rada Massarwa1, Suhair Hanna6, Ido Amit5, Erez Y Levanon4, Ninette Amariglio7, Noam Stern-Ginossar1, Noa Novershtern8, Gideon Rechavi9, Jacob H Hanna8.
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 N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A 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. m(6)A 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.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25569111 DOI： 10.1126/science.1261417
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728