m6A mRNA methylation by METTL14 regulates early pancreatic cell differentiation

EMBO J. 2024 Nov;43(22):5445-5468. doi: 10.1038/s44318-024-00213-2. Epub 2024 Sep 25.

Abstract

N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA and plays important roles in human and mouse embryonic stem cell pluripotency, maintenance, and differentiation. We have recently reported that m6A is involved in the postnatal control of β-cell function in physiological states and in type 1 and 2 diabetes. However, the precise mechanisms by which m6A acts to regulate the development of human and mouse pancreas are unexplored. Here, we show that the m6A landscape is dynamic during human pancreas development, and that METTL14, one of the m6A writer complex proteins, is essential for the early differentiation of both human and mouse pancreatic cells.

Keywords: Duct Cells; Human Pancreas Development; m6A mRNA Methylation; α-cells; β-cells.

MeSH terms

  • Adenosine* / analogs & derivatives
  • Adenosine* / genetics
  • Adenosine* / metabolism
  • Animals
  • Cell Differentiation* / genetics
  • Humans
  • Methylation
  • Methyltransferases* / genetics
  • Methyltransferases* / metabolism
  • Mice
  • Pancreas* / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism

Substances

  • Methyltransferases
  • METTL14 protein, human
  • RNA, Messenger
  • Adenosine
  • N-methyladenosine
  • Mettl14 protein, mouse