m6A RNA methylation impacts fate choices during skin morphogenesis. Academic Article uri icon

Overview

abstract

  • N6-methyladenosine is the most prominent RNA modification in mammals. Here, we study mouse skin embryogenesis to tackle m6A's functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting with in vivo ribosomal profiling, we unearth a correlation between m6A modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transcriptomics and bioinformatics, both signaling and canonical translation pathways show significant downregulation after m6A loss. Interestingly, however, many highly m6A-modified mRNAs are markedly upregulated upon m6A loss, and they encode RNA-methylation, RNA-processing and RNA-metabolism factors. Together, our findings suggest that m6A functions to enhance translation of key morphogenetic regulators, while also destabilizing sentinel mRNAs that are primed to activate rescue pathways when m6A levels drop.

publication date

  • August 26, 2020

Research

keywords

  • Adenosine
  • Organogenesis
  • RNA, Messenger
  • Skin

Identity

PubMed Central ID

  • PMC7535931

Scopus Document Identifier

  • 85090669179

Digital Object Identifier (DOI)

  • 10.1186/s12935-019-1045-1

PubMed ID

  • 32845239

Additional Document Info

volume

  • 9