N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency

Cell. 2015 Jun 4;161(6):1388-99. doi: 10.1016/j.cell.2015.05.014.

Abstract

N(6)-methyladenosine (m(6)A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m(6)A-modified mRNA is regulated by an m(6)A reader protein, human YTHDF2, which recognizes m(6)A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that another m(6)A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereas YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m(6)A. Therefore, the m(6)A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Peptide Initiation Factors / metabolism
  • Protein Biosynthesis*
  • RNA Stability
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomes / metabolism

Substances

  • Peptide Initiation Factors
  • RNA, Messenger
  • RNA-Binding Proteins
  • YTHDF1 protein, human
  • YTHDF2 protein, human
  • N6-methyladenosine (m6A)
  • Adenosine

Associated data

  • GEO/GSE63591