Mechanisms and Strategies for Determining m 6 A RNA Modification Sites by Natural and Engineered m 6 A Effector Proteins.

N 6 -Methyladenosine (m 6 A) is the most common internal RNA modification in the consensus sequence of 5'-RRACH-3'. The methyl mark is added by writer proteins (METTL3/METTL14 metyltransferase complex) and removed by eraser proteins (m 6 A demethylases; FTO and ALKBH5). Recognition of this methyl mark by m 6 A reader proteins leads to changes in RNA metabolism. How the writer and eraser proteins determine their targets is not well-understood, despite the importance of this information in understanding the regulatory mechanisms and physiological roles of m 6 A. However, approaches for targeted manipulation of the methylation state at specific sites are being developed. In this review, I summarize the recent findings on the mechanisms of target identification of m 6 A regulatory proteins, as well as recent approaches for targeted m 6 A modifications.