From: Epigenetic modification of m6A regulator proteins in cancer
Types | m6A Regulator | Full names | Cellular localization | Function | Ref |
---|---|---|---|---|---|
Writers | METTL3 | Methyltransferase-like 3 | Nucleus | Catalyzes methylation reaction/Catalyzes m6A modifcation | |
WTAP | Wilms tumor 1- associated protein | Nucleus | Promotes METTL3-METTL14 heterodimer localization into nuclear speckles | ||
METTL14 | Methyltransferase-like 14 | Nucleus | Assists METTL3 to recognize the subtract | ||
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 | ||
RBM15 | RNA binding motif protein 15 | Nucleus | Directs METTL3-METTL14 heterodimer to specifc RNA sites | ||
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) | ||
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 | ||
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 | ||
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 | |
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” | ||
HNRNPG | Heterogeneous nuclear ribonucleoprotein G | Nucleus | Mediates mRNA splicing and maturity | ||
YTHDC1 | YTH domain containing 1 | Nucleus | Promotes mRNA splicing and transcriptional silencing; regulates RNA nuclear export and splicing | ||
YTHDF3 | YTH N6-methyladenosine RNA binding protein 3 | Cytosol | Interacts with YTHDF1 to promote mRNA translation or interacts with YTHDF2 to promote mRNA degradation | ||
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 | ||
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] |