TABLE 1.
Main functions of the three major groups of m6A-related proteins.
| Category | Proteins | Main functions | References |
|---|---|---|---|
| Writers | METTL3 | Catalyzes m6A formation | Tong et al. (2018a); Zhang et al. (2019) |
| METTL14 | Promotes the catalytic activity of METTL3 | Wang et al. (2016); Batista (2017); Tong et al. (2018a); Zaccara et al. (2019); Zhang et al. (2019) | |
| WTAP | Ensures proper localization of the METTL3-METTL14 complex | Ping et al. (2014); Zhang et al. (2019) | |
| Recruits target RNAs and other functional factors | Zhang et al. (2019) | ||
| VIRMA | Mediates m6A deposition at specific regions of target mRNAs | Yue et al. (2018) | |
| RBM15/15B | Recruits the writer complex to specific regions | Patil et al. (2016) | |
| Modulates m6A deposition on XIST | Patil et al. (2016) | ||
| METTL16 | Installs m6A on snRNAs and mRNAs to regulate SAM homeostasis | Pendleton et al. (2017) | |
| CBLL1 | Interacts with WTAP | Růžička et al. (2017) | |
| ZC3H13 | Facilitates the nuclear localization of the writer complex | Knuckles et al. (2018); Wen et al. (2018) | |
| ZCCHC4 | Installs a single m6A modification on rRNA | Pinto et al. (2020) | |
| Modulates mRNA translation | Ma et al. (2019) | ||
| Erasers | FTO | Removes m6A | Jia et al. (2011) |
| Removes m6Am | Mauer et al. (2019) | ||
| Demethylates other sites in certain snRNAs and specific tRNAs | Wang et al. (2014); Mauer et al. (2019) | ||
| ALKBH5 | Removes m6A | Zheng et al. (2013) | |
| Targets ncRNAs separately from mRNAs | Wang et al. (2014) | ||
| Participates in germ cell development | Zheng et al. (2013) | ||
| Modulates RNA metabolism and nuclear RNA export | Zheng et al. (2013); Zhang et al. (2017a) | ||
| FMN | A newly identified artificial molecular demethylase | Xie et al. (2019) | |
| Readers | YTHDF1 | Promotes the efficient translation of target mRNAs | Meyer et al. (2015); Wang et al. (2015) |
| YTHDF2 | Accelerates RNA degradation and inhibits the translation of mRNAs | Meyer et al. (2015); Wang et al. (2015) | |
| YTHDF3 | Promotes RNA translation with YTHDF1 | Shi et al. (2017) | |
| Inhibits the translation of mRNAs with YTHDF2 | Shi et al. (2017) | ||
| YTHDC1 | Modulates alternative RNA splicing | Xiao et al. (2016) | |
| Regulates nuclear export | Xiao et al. (2016) | ||
| Accelerates the decay of transcripts to maintain SAM levels | Shima et al. (2017) | ||
| Suppresses gene expression involving X chromosome inactivation | Patil et al. (2016) | ||
| YTHDC2 | Promotes the efficient translation of its target transcripts | Kretschmer et al. (2018) | |
| Mediates the subsequent degradation of its target transcripts | Kretschmer et al. (2018) | ||
| IGF2BPs | Regulates the stability, localization and translation of target RNAs | Degrauwe et al. (2016); Huang et al. (2018) | |
| EIF3 | Initiates and promotes cap-independent translation | Meyer et al. (2015) | |
| HNRNPA2B1 | Modulates alternative splicing | Alarcón et al. (2015a) | |
| Promotes mature miRNA biogenesis | Alarcón et al. (2015a); Coker et al. (2019) | ||
| HNRNPC | Involved in premRNA processing, including splicing | Liu et al. (2015) | |
| HNRNPG | Involved in premRNA processing, including splicing | Liu et al. (2017) |
ALKBH5, ALKB homolog 5; CBLL1, Casitas B-lineage lymphoma-transforming sequence-like protein 1; FMN, flavin mononucleotide; FTO, fat mass and obesity-associated protein; HNRNPA2B1/C/G, heterogeneous nuclear ribonucleoprotein A2B1/C/G; METTL3/14/16, methyltransferase-like 3/14/16; IGF2BPs, insulin-like growth factor 2 binding proteins; RBM15/15B, RNA binding motif protein 15/15B; VIRMA, Vir-like m6A methyltransferase associated; WTAP, Wilms tumor 1-associated protein; YTHDF1/2/3, YTH domain-containing family 1/2/3, YTHDC1/2, YTH domain-containing 1/2; ZC3H13, zinc finger CCCH domain-containing protein 13; ZCCHC4, zinc finger CCHC-type containing 4.