Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism

Abstract

N⁶-methyladenosine (m⁶A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m⁶A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m⁶A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.

Fig. 1

Diverse molecular functions of m⁶A. In eukaryotic cells, RNA m⁶A level is dynamically regulated by “writers” and “erasers”, and recognized by “readers” in direct or indirect ways. The diversity of cellular processes involving m⁶A is mainly contributed by various “readers”. The nuclear m⁶A modulates a mRNA alternative splicing,^{,–,–,,–} b secondary structure switching,^,, c mRNA export,^, d pri-miRNA processing,^, e mRNA stability and f XIST-dependent X chromosome inactivation, while the cytoplasmic m⁶A (g and h) enhances mRNA translation efficiency^,,,, and i accelerates mRNA decay.^,,,

Fig. 2

Schematic summary of the roles of m⁶A in regulating mRNA splicing. Exonic and most intronic m⁶A sites promotes exon inclusion while a small proportion of intronic m⁶A sites can also lead to exon skipping through a refined buffering system composed of its writers, readers, erasers as well as other splicing-related factors