Table 1 The function of m⁶A modifcation regulators (m⁶A methylation enzymes) in RNA metabolism

Writers

METTL3

Methyltransferase-like 3

Nucleus

Catalyzes methylation reaction/Catalyzes m6A modifcation

[5, 20, 21]

WTAP

Wilms tumor 1- associated protein

Nucleus

Promotes METTL3-METTL14 heterodimer localization into nuclear speckles

[22, 23]

METTL14

Methyltransferase-like 14

Nucleus

Assists METTL3 to recognize the subtract

[20, 22]

VIRMA (KIAA1429)

Vir-like m6A methyltransferase associated

Nucleus

Recruits the m6A complex to the special RNA site and interacts with polyadenylation cleavage factors CPSF5 and CPSF6

[24, 25]

RBM15

RNA binding motif protein 15

Nucleus

Directs METTL3-METTL14 heterodimer to specifc RNA sites

[24, 26]

RBM15B

RNA binding motif protein 15B

Nucleus

Directs METTL3-METTL14 heterodimer to specifc RNA sites

METTL16

Methyltransferase-like 16

Nucleus

Catalyzes m6 A modifcation; mediate the m6A methylation of U6 snRNA, noncoding RNAs, and precursor mRNAs (premRNAs)

[27,28,29]

ZC3H13

Zinc finger CCCH-type containing 13

Nucleus

Bridges WTAP to the mRNA-binding factor Nito;Anchors WTAP in the nucleus to enhance m6A modifcation

[30, 31]

METTL5

Methyltransferase-like 5

Nucleus

Induce the m6A methylation of 18 S rRNA

[32]

ZCCHC4

Zinc finger CCHC-type containing 4

Nucleus

An m6A methyltransferase of 28 S rRNA mediating ribosomal RNA methylation

[33,34,35]

METTL4

Methyltransferase-like 4

Nucleus

Mediates the m6A methylation of U2 snRNA to regulate pre-mRNA splicing

[36]

Erasers

FTO

Fat mass and obesity

-associated protein

Nucleus

Acts as m6A demethylase to promote mRNA splicing and translation; removes m6A modification

[37]

ALKBH5

AlkB homologue 5

Nucleus

Removes m6A modifcation to promote mRNA nuclear processing and mRNA export

[38]

ALKBH3

AlkB homologue 3

Nucleus

Remove m6 A modifcation level

[39]

Readers

YTHDF2

YTH N6-methyladenosine RNA binding protein 2

Cytosol

Promotes mRNA degradation

[40, 41]

YTHDF1

YTH N6-methyladenosine RNA binding protein 1

Cytosol

Promotes mRNA translation initiation

[42]

eIF3

Eukaryotic translation initiation factor 3 subunit A

Cytosol

Promotes mRNA translation

[43]

HNRNPA2B1

Heterogeneous nuclear ribonucleoprotein A2/B1

Nucleus

Promotes primary miRNA processing and mRNA splicing; promotes primary microRNA processing and mediates nuclear accumulation

[44]

HNRNPC

Heterogeneous nuclear ribonucleoprotein C

Nucleus

Mediates mRNA splicing and maturity

Interacts with m6A-modifed mRNA and affects its enrichment and splicing, generating a phenomenon termed the “m6A switch”

[45, 46]

HNRNPG

Heterogeneous nuclear ribonucleoprotein G

Nucleus

Mediates mRNA splicing and maturity

[45, 46]

YTHDC1

YTH domain containing 1

Nucleus

Promotes mRNA splicing and transcriptional silencing; regulates RNA

nuclear export and splicing

[47, 48]

YTHDF3

YTH N6-methyladenosine RNA binding protein 3

Cytosol

Interacts with YTHDF1 to promote mRNA translation or

interacts with YTHDF2 to promote mRNA degradation

[49, 50]

YTHDC2

YTH domain containing 2

Nucleus; cytosol

Improves the translation efciency of target mRNA

[51]

IGF2BP1

Insulin-like growth factor 2 mRNA binding protein 1

Nucleus; cytosol

Promotes the stability and translation of mRNA

[52]

IGF2BP2

Insulin-like growth factor 2 mRNA binding protein 2

Nucleus; cytosol

Promotes the stability and translation of mRNA

[52]

IGF2BP3

Insulin-like growth factor 2 mRNA binding protein 3

Nucleus; cytosol

Promotes the stability and translation of mRNA

[52]

FMRP

Fragile X mental retardation protein

Nucleus; cytosol

Promote the nuclear export and stability of m6A-modifed RNAs

[53, 54]

PRRC2A

Proline rich coiled-coil 2 A

Cytosol

Bind to a consensus GGACU motif in the Olig2 coding sequence to stabilize Olig2 mRNA

[46]

RBM33

RNA-binding motif protein 33

Nucleus

Forms a complex with ALKBH5 and mediates m6 A demethylation of selected transcripts by regulating ALKBH5 substrate accessibility and activity

[55]