PLX126154

GSE61994: m6A RNA Methylation is Critical for Adequate Exit from Nave Pluripotency and Execution of Mammalian Development (3p-Seq)

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

In this study we identify Mettl3, an m6A RNA modification writer, as a critical regulator for terminating nave pluripotency and a positive maintainer of primed pluripotency in vitro and in vivo. Remarkably, Mettl3 knockout pre-implantation epiblasts and nave ES cells, entirely lack m6A on coding mRNAs and are viable. Yet, they fail to adequately terminate the nave pluripotent state, and subsequently undergo aberrant priming and early lineage commitment at the post-implantation stage. A comprehensive functional and genomic analysis involving profiling of m6A, RNA transcription and translation in Mettl3 wild-type and knockout pluripotent and differentiated cells, identified m6A as a critical determinant that destabilizes secondary nave specific pluripotency genes Esrrb, Klf4 and Nanog, and restrains their transcript stability and translation efficiency. In summary, our findings provide for the first time evidence for a critical role for an mRNA epigenetic modification in early mammalian development in vivo, and identify a mechanism that functionally regulates mouse nave and primed pluripotency in an opposing manner. SOURCE: Noa Novershtern (noa.novershtern@weizmann.ac.il) - Weizmann Institute of Science