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.

Structural and functional characterization of the proteins responsible for N6-methyladenosine modification and recognition.

More than 100 types of RNA modifications have been identified so far, which are involved in a variety of cellular processes. N6-methyladenosine (m6A), as one most abundant RNA modification, is found in several RNA species, and mainly located in the stop codons, long internal exons as well as 3'UTR. It was reported that m6A modification is preferred after G in the conserved sequence RRm6ACH (R = A/G and H = A/C/U). There are two families of enzymes responsible for maintaining the balance of m6A methylation: RNA methyltransferases and demethylases, which add and remove methyl marks from RNA, respectively. METTL3 complex, the m6A RNA methyltransferase, has been identified, and two kinds of demethylases are characterized thus far, including Fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5). Besides the "writers" and "erasers" for m6A, m6A specific recognizing protein, such as the YTH domain, also has attracted significant attention. Herein, we will focus on the recent progress in understanding biological/biochemical functions and structures of proteins responsible for the m6A RNA modification and recognition. Detailed analysis of these important proteins will guide us in designing target-specific small molecule chemical probes and inhibitors.