M⁶A RNA methylation orchestrates transcriptional dormancy during paused pluripotency.

ABSTRACT: Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that N⁶-methyladenosine (m⁶A) RNA methylation by Mettl3 is required for developmental pausing in mouse blastocysts and embryonic stem (ES) cells. Mettl3 enforces transcriptional dormancy through two interconnected mechanisms: (1) it promotes global mRNA destabilization and (2) it suppresses global nascent transcription by destabilizing the mRNA of the transcriptional amplifier and oncogene N-Myc, which we identify as a crucial anti-pausing factor. Knockdown of N-Myc rescues pausing in Mettl3^-/- ES cells, an

SUBMITTER: Collignon E 

PROVIDER: S-EPMC11619322 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature