Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.
Science
; 347(6225): 1002-6, 2015 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-25569111
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Diferenciação Celular
/
Adenosina
/
Células-Tronco Pluripotentes
/
Metiltransferases
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article