METTL3-dependent m6A RNA methylation regulates transposable elements and represses human naive pluripotency through transposable element-derived enhancers.

ABSTRACT: N 6-methyladenosine (m6A) is the most prevalent messenger RNA modification with diverse regulatory roles in mammalian cells. While its functions are well-documented in mouse embryonic stem cells (mESCs), its role in human pluripotent stem cells (hPSCs) remains to be fully explored. METTL3 is the main enzyme responsible for m6A deposition. Here, using a METTL3 inducible knockout (iKO) system, we uncovered that, unlike in mESCs, METTL3 was indispensable for hPSC maintenance. Importantly, loss of METTL3 caused significant upregulation of pluripotency factors including naïve pluripotency genes and failure to exit pluripotency, thus impairing stem cell differentiation towards both embryonic and extraembryonic cell lineages. Mechanistically, METTL3 iKO in hPSCs promoted expression and enhancer a

SUBMITTER: Zhang W 

PROVIDER: S-EPMC12038396 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature