YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs

N(6)-methyladenosine (m(6)A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m(6)A-selective ‘reader’ proteins of the YTH family, which incorporate m(6)A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m(6)A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m(6)A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m(6)A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.