2. Academic Validation
  3. N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency

N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency

  • Cell. 2015 Jun 4;161(6):1388-99. doi: 10.1016/j.cell.2015.05.014.
Xiao Wang 1,  Boxuan Simen Zhao 1,  Ian A Roundtree 2,  Zhike Lu 1,  Dali Han 1,  Honghui Ma 1,  Xiaocheng Weng 1,  Kai Chen 1,  Hailing Shi 1,  Chuan He 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • 2 Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • 3 Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. Electronic address: [email protected].
PMID: 26046440 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.

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