Table 2. Summary of the main evidence of the effect of m6A regulators on RNA metabolism and the subcellular location of each m6A regulator.
| Classification of m6A regulators | Symbol of the regulators | Sub-cellular location | Biological function in the metabolism of RNAs | Reference |
|---|---|---|---|---|
| Readers | YTHDF2 | Cytoplasm | Mediating the intracellular RNA degradation by co-localizing with DCP1a, GW182, and DDX6, which are the component of RNA degradation related P-bodies | (23) |
| YTHDF1 | Cytoplasm | Accelerating the protein translation process by recruiting ribosomes and eIF3 to transcripts | (24,25) | |
| YTHDC1 | Nucleus | YTHDC1 can combine with SAM68, SC35, and SRSF, mediating the alternative splicing. Besides, the YTHDC1 can bind to the SRSF3 protein leading to the transportation of mRNA from nucleus to cytoplasm by binding NXF1 protein. YTHDC1 knock out witnessed no significant change in m6A/A ratios by LC-MS/MS, but in situ fluorescence hybridization reported increased m6A-methylated transcripts which is NXF1 independent. Over-expression of YTHDC1 decreased m6A-methylated mRNA transcripts in the nucleus but did not increase the number of m6A-methylated transcripts in the cytoplasm. YTHDC1 is also involved in intranuclear degradation of m6A-labeled mRNA | (26-30) | |
| Writer | METTL3 | Nucleus | METTL3 homolog Ime4 in Drosophilia is involved in alternating splicing of sex-lethal gene of drosophila, SXL. METTL3 can also interact with eIF4A2 to facilitate gene expression | (31,32) |
| WTAP, KIAA1429, and RBM15/RBM15B | Nucleus | There is evidence that splicing regulators such as Fl(2)D, Virilizer33, and Spenito (Nito) are homologous to the mammalian m6A methylation transferases. However, whether m6A modification is distributed near introns or exons close to the alternative splicing site is difficult to determine. | (33-35) | |
| Eraser | FTO | Nucleus | The deletion of FTO improves the mRNA binding capacity of SRSF2 resulting in an increase in the expression of the target exon. FTO is also involved in the RNA precursor splicing process | (36-38) |
| ALKBH5 | Nucleus | ALKBH5 co-locate with ASF/SF2, and these molecules not only regulate the variable splicing of precursor RNA | (39-42) |
YTHDF1/2, YTH domain family 1/2; YTHDC1, YTH domain containing 1; eIF, eukaryotic initiation factor; SAM68, Src-associated in mitosis 68KD; SRSF, serine/arginine-rich splicing factor; NXF1, nuclear RNA export factor 1; m6A, N6-adenosine methylation; LC-MS/MS, liquid chromatography coupled to tandem mass spectrometry; WTAP, Wilms tumor 1-associating protein; FTO, fat mass and obesity-associated gene; ALKBH5, AlkB homolog 5.