YTH Domain: A Family of N(6)-methyladenosine (m(6)A) Readers

Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N(6)-methyladenosine (m(6)A) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, m(6)A can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the m(6)A modification is reversible and dynamic. Moreover, m(6)A is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m(6)A recognition by YTH domain-containing proteins, which would shed new light on m(6)A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.