N6-methyladenosine Modulates Messenger RNA Translation Efficiency

Summary

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 m⁶A 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.