| Summary: | Cells of a multicellular organism share identical DNA sequence, yet their fates and functions diverge substantially. Epigenetics studies chemical reactions and factors that determine cell fates without changing the DNA sequence. Established epigenetic mechanisms involve chemical modifications of DNA and histone proteins. In contrast, RNAs carry numerous chemical modifications whose potential roles in epigenetic processes have not been explored. N6-methyladenosine (m6A) is the most prevalent modification present in the messenger RNA of all higher eukaryotes. This modification is reversible and non-stoichiometric, and adds an additional layer to the dynamic control of mRNA metabolism. We characterized two m 6A reader proteins, human YTHDF1 and YTHDF2, which specifically recognize m6A-modified mRNAs inside the cells. In a unified mechanism of m6A-based gene regulation, YTHDF2 reduces mRNA stability to control the lifetime of target RNAs, whereas, YTHDF1 promotes mRNA translation to ensure effective protein production from short-lived RNAs marked by m 6A. Therefore, the m6A modification in mRNA endows gene expression with fast response and controllable protein production. Such mechanism of gene regulation is found critical during epigenetic processes, e.g. stem cell differentiation and animal development.
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