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

Authors: Dai, Xiaoxia; Wang, Tianlu; Gonzalez, Gwendolyn; Wang, Yinsheng

Published In Anal Chem, (2018 Jun 05)

Abstract: N1-methyladenosine (m1A) is an important post-transcriptional modification in RNA; however, the exact biological role of m1A remains to be determined. By employing a quantitative proteomics method, we identified multiple putative protein readers of m1A in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to m1A in RNA. We also found that Trp432 in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N6-methyladenosine (m6A), is required for its recognition of m1A. An analysis of previously published data revealed transcriptome-wide colocalization of YTH domain-containing proteins and m1A sites in HeLa cells, suggesting that YTH domain-containing proteins can bind to m1A in cells. Together, our results uncovered YTH domain-containing proteins as readers for m1A in RNA and provided new insight into the functions of m1A in RNA biology.

PubMed ID: 29791134

MeSH Terms: Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism*; Adenosine/analogs & derivatives*; Adenosine/chemistry; Adenosine/metabolism; Binding Sites; HEK293 Cells; HeLa Cells; Humans; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/metabolism*; Protein Binding; Protein Domains; RNA Helicases; RNA Splicing Factors/chemistry; RNA Splicing Factors/metabolism*; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/metabolism*; RNA/chemistry; RNA/metabolism*