Structural and Functional Characterization of the Proteins Responsible for N(6)-Methyladenosine Modification and Recognition.

RNA modification, involving in a wide variety of cellular processes, has been identified over 100 types since 1950s. N(6)-methyladenosine (m6A), as one of the most abundant RNA modifications, is found in several RNA species and predominantly located in the stop codons, long internal exons as well as 3'UTR. It was reported that m6A modification preferentially appears after G in the conserved motif RRm6ACH (R = A/G and H = A/C/U). There are two families of enzymes responsible for maintaining the balance of m6A modification: m6A methyltransferases and demethylases, which add and remove methyl marks for adenosine of RNA, respectively. METTL3 complex, the m6A methyltransferases, and two kinds of demethylases including Fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5) are characterized thus far. Besides the "writers" and "erasers", m6A specific recognizing proteins, such as the YTH (YT521-B homology) domain family proteins, also have attracted significant attention. Herein, we focus on the recent progress in understanding the biological/biochemical functions and structures of proteins responsible for the m6A modification and recognition. Detailed analyses of these important proteins are essential for the further study of their biological function and will also guide us in designing more potent and specific small-molecule chemical inhibitors for these targets.