Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons

ACS Chem Biol. 2020 Aug 21;15(8):2087-2097. doi: 10.1021/acschembio.0c00265. Epub 2020 Jul 20.

Abstract

N6-methyladenosine (m6A), a conserved epitranscriptomic modification of eukaryotic mRNA (mRNA), plays a critical role in a variety of biological processes. Here, we report that m6A modification plays a key role in governing direct lineage reprogramming into induced neuronal cells (iNs). We found that m6A modification is required for the remodeling of specific mRNAs required for the neuronal direct conversion. Inhibition of m6A methylation by Mettl3 knockdown decreased the efficiency of direct lineage reprogramming, whereas increased m6A methylation by Mettl3 overexpression increased the efficiency of iN generation. Moreover, we found that transcription factor Btg2 is a functional target of m6A modification for efficient iN generation. Taken together, our results suggest the importance of establishing epitranscriptomic remodeling for the cell fate conversion into iNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Animals
  • Cell Lineage
  • Cells, Cultured
  • Cellular Reprogramming
  • Epigenesis, Genetic
  • Mice
  • Neurons / cytology*
  • RNA, Messenger / genetics
  • Transcriptome*

Substances

  • RNA, Messenger
  • N-methyladenosine
  • Adenosine