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. 2021 Jun 8;23(11):2269–2279. doi: 10.1007/s12094-021-02644-3

Table 1.

Characteristics and functions of m6A enzymes in RNA metabolism

Category Gene Characteristics and functions References
Writers METTL3 Promotes formation of the methyltransferase complex, installs m6A on RNA, and catalyzes m6A modification [14, 22, 25]
METTL14 Catalyzes the methylation reaction, mediates protein–protein interaction, and helps METTL3 recognize the special RNA substrate [22, 25]
METTL16

A homologue of METTL3

Regulator of cellular SAM levels and methylator of U6 small nuclear RNA

[31, 32]
WTAP

Contributes to the localization of METTL3-METTL14 heterodimer to the nuclear speckle

Recruits target RNA for m6A modification

Enhances the catalytic capacity of the writer

[26]
RBM15/15B Binds the m6A complex and recruit it to special RNA site [27, 28]
VIRMA Recruits the m6A complex to a special RNA site where it interacts with polyadenylation cleavage factors CPSF5 and CPSF6 [30]
ZC3H13 Bridges WTAP to the mRNA-binding factor to enhance m6A [29]
Erasers FTO Reverses RNA modification and controls cellular homeostasis [33, 35]
ALKBH5

Maintains the balance of m6A levels within the transcriptome

Contributions to in alkylated DNA repair

[34, 35]
ALKBH3

Performs its demethylation function on tRNA rather than mRNA or rRNA

Generally considered to serve as a DNA repair enzyme

[37]
Readers YTH family First five characterized m6A readers
YTHDC1

Contributes to RNA splicing and export

Plays a critical role in the pre-mRNA processing

[40]
YTHDC2 Enhances the translation of target RNA but also reduces the abundance of target RNA [41]
YTHDF1 Enhances mRNA translation [43]
YTHDF2 Promotes mRNA degradation [44]
YTHDF3 Enhances translation and degradation by interacting with YTHDF1 and YTHDF2 [45]
HNRNP family Another group of RNA-binding proteins
HNRNPA2B1 Mediates miRNA processing by recruiting a microprocessor complex upon binding to the m6A [45, 47]
HNRNPC/HNRNPG Mediate selective splicing of m6A-modified transcripts, but do so through direct interaction whit m6A-dependent structural switches [45]
eIF3 Initiates the translation procedure by binding to the m6A site in the 5’-UTR of mRNA [48]
IGF2BPs Stabilizes the target gene [48]
Prrc2a Stabilizes mRNA expression by binding to a consensus GGACU motif in the coding sequence in an m6A-dependent manner [49]