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

TLDR

mRNA modification regulates pluripotency by enabling molecular switches that dismantle the transcription factor network during differentiation. The study demonstrates that N6‑methyladenosine on pluripotency transcripts drives the transition from naïve pluripotency to differentiation. m6A methylation destabilizes pluripotency transcripts, reduces their translation, accelerates decay of naïve pluripotency, and is essential for mammalian development. Geula et al., Science, this issue p.

Abstract

mRNA modification regulates pluripotency When stem cells progress from an embryonic pluripotent state toward a particular lineage, molecular switches dismantle the transcription factor network that keeps the cell pluripotent. Geula et al. now show that N6-methyladenosine (m6A), a messenger RNA (mRNA) modification present on transcripts of pluripotency factors, drives this transition. Methylation destabilized mRNA transcripts and limited their translation efficiency, which promoted the timely decay of naïve pluripotency. This m6A methylation was also critical for mammalian development. Science , this issue p. 1002