m  6  A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation

Geula, Shay; Moshitch-Moshkovitz, Sharon; Dominissini, Dan; Mansour, Abed AlFatah; Kol, Nitzan; Salmon‐Divon, Mali; Hershkovitz, Vera; Peer, Eyal; Mor, Nofar; Manor, Yair S.; Ben-Haim, Moshe Shay; Eyal, Eran; Yunger, Sharon; Pinto, Yishay; Jaitin, Diego Adhemar; Viukov, Sergey; Rais, Yoach; Krupalnik, Vladislav; Chomsky, Elad; Zerbib, Mirie; Maza, Itay; Rechavi, Yoav; Massarwa, Rada; Hanna, Suhair; Amit, Ido; Levanon, Erez Y.; Amariglio, Ninette; Stern‐Ginossar, Noam; Novershtern, Noa; Rechavi, Gideon; Hanna, Jacob H.

doi:10.1126/science.1261417

articleScienceJan 2, 2015BRONZE OA

m 6 A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation

SGShay Geula SMSharon Moshitch-Moshkovitz DDDan Dominissini AAAbed AlFatah Mansour NKNitzan Kol

Weizmann Institute of Science · Sheba Medical Center · +3 more institutions

PubMed

Indexed incrossrefpubmed

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…

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Topics & keywords

Topics

Keywords

Methylation
Messenger RNA
Embryonic stem cell
Induced pluripotent stem cell
Cell biology
Biology
Molecular biology
Transcription (linguistics)

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