N6-methyladenosine modulates messenger RNA translation efficiency

Abstract

N6-methyladenosine (m6A) 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 m6A-modified mRNA is regulated by an m6A reader protein, human YTHDF2, which recognizes m6A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that another m6 A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m6A-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 m6A. Therefore, the m6A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.