Mechanisms and Strategies for Determining m6A RNA Modification Sites by Natural and Engineered m6A 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.