Identification of YTH Domain-Containing Proteins as the Readers for N1-Methyladenosine in RNA.

N1-methyladenosine (mA) is an important post-transcriptional modification in RNA; however, the exact biological role of mA remains to be determined. By employing a quantitative proteomics method, we identified multiple putative protein readers of mA in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to mA in RNA. We also found that Trp in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N-methyladenosine (mA), is required for its recognition of mA. An analysis of previously published data revealed transcriptome-wide colocalization of YTH domain-containing proteins and mA sites in HeLa cells, suggesting that YTH domain-containing proteins can bind to mA in cells. Together, our results uncovered YTH domain-containing proteins as readers for mA in RNA and provided new insight into the functions of mA in RNA biology.