m6A methylation in the perinatal field

Abstract

N6-methyladenosine (m6A), a major modification of messenger RNA (mRNA) and long non-coding RNA, plays critical roles in RNA metabolism and function [1]. Among the many types of RNA modification, m6A is the most frequent and abundant chemical post-transcriptional RNA modification [2]. Methylated RNA immunoprecipitation followed by sequencing (MeRIP-Seq) is a comprehensive assay to determine the presence of m6A [1]. Since the development of this assay, the functions of m6A have gradually become clearer m6A within coding mRNA are most abundantly observed in the vicinity of the stop codon, especially within the 3'UTR, and they have a consensus sequence of RRACH, where R is a purine and H is any base except for G [1]. m6A is involved in post-transcriptional regulation, especially in determining the stability and lifespan of mRNA [3]. Furthermore, several m6A regulators have been reported, such as the methylating enzyme m6A writer proteins (METTL3, METTL14, METTL16, WTAP), the demethylating enzyme m6A eraser proteins (FTO, ALKBH5), and m6A reader proteins (YTH family) that recognize m6A [3]. The m6A site in mRNA of the same gene differs between cell and tissue types; m6A levels change in response to external stimuli, thereby functioning as a dynamic type of modification that fine-tunes gene expression [4]. Notably, although the levels of mRNA (arising from gene expression) and protein are positively correlated, the correlation is weak; it is not a perfect correlation [5]. Therefore, elucidation of post-transcriptional mRNA regulation through m6A modifications can help clarify the role of genes involved in various cellular events.