作者
Shay Geula, Sharon Moshitch-Moshkovitz, Dan Dominissini, Abed AlFatah Mansour, Nitzan Kol, Mali Salmon-Divon, Vera Hershkovitz, Eyal Peer, Nofar Mor, Yair S Manor, Moshe Shay Ben-Haim, Eran Eyal, Sharon Yunger, Yishay Pinto, Diego Adhemar Jaitin, Sergey Viukov, Yoach Rais, Vladislav Krupalnik, Elad Chomsky, Mirie Zerbib, Itay Maza, Yoav Rechavi, Rada Massarwa, Suhair Hanna, Ido Amit, Erez Y Levanon, Ninette Amariglio, Noam Stern-Ginossar, Noa Novershtern, Gideon Rechavi, Jacob H Hanna
发表日期
2015/2/27
期刊
Science
卷号
347
期号
6225
页码范围
1002-1006
出版商
American Association for the Advancement of Science
简介
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.
引用总数
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