Table 1.
Substrate specificities and kinetic parameters in m6A RNA modification for writers, readers, and erasers.
| Writers | Substrate | Km (Substrate) | Km (SAM) | KD(1) | KD(2) | kcat | References |
|---|---|---|---|---|---|---|---|
| METTL3/METTL14 | DRACH (D = A,G,U; R = A,G; H = A,C,U) | 22 ± 2 nM | 102 ± 15 nM | n/a | n/a | 18 ± 2 h−1 | Liu et al (2014) and Li et al (2016) |
| WTAP/VIRMA | human ACTB mRNA fragment | n/a | n/a | 826.3 ± 336.0 nM | n/a | n/a | Su et al (2022) |
| WTAP/VIRMA/HAKAI | human ACTB mRNA fragment | n/a | n/a | 562.7 ± 76.6 nM | n/a | n/a | Su et al (2022) |
| WTAP/VIRMA/ZC3H13 | human ACTB mRNA fragment | n/a | n/a | 256.3 ± 27.9 nM | n/a | n/a | Su et al (2022) |
| WTAP/VIRMA/ZC3H13/HAKAI | human ACTB mRNA fragment | n/a | n/a | 214.0 ± 2.6 nM | n/a | n/a | Su et al (2022) |
| METTL16 | UACAGARAA (U6 snRNA, MALAT1) | ˜10 µM | >0.4 mM | 18 ± 7 µM | 126 ± 6 µM | 0.07 ± 0.02 min−1 | Warda et al (2017), Yu et al (2021b), and Breger and Brown (2023) |
| METTL5/TRMT112 | A1832 of 18S rRNA | 1.1 ± 0.2 μM (pH 8.0) | 1.0 ± 0.2 μM (pH 8.0) | n/a | n/a | 13.1 ± 0.8 h−1 (pH 8.0) | van Tran et al (2019) and Yu et al (2021b) |
| ZCCHC4 | A4220 of 28S rRNA | n/a | 6.7 μM | n/a | n/a | n/a | Ren et al (2019) |
| PCIF/CAPAM | m7GpppAm | 3.5 ± 0.71/0.3 ± 0.03 μM (pH 8.0) | 0.65 ± 0.05 μM (pH 8.0) | n/a | n/a | 0.67 ± 0.01 min−1 (pH 8.0) | Akichika et al (2019), Boulias et al (2019), and Yu et al (2021b) |
| Readers | References | ||||||
| YTHDC1 | G G m6A C/G G/A/U | n/a | n/a | 0.39 ± 0.071 µM | n/a | n/a | Arguello et al (2019) |
| YTHDC2 | G G m6A C/U A/G/C/U | n/a | n/a | 321.6 ± 61.9 nM | n/a | n/a | Hsu et al (2017) |
| YTHDF1 | C/G U/G/C m6A G/C/U A/G/C/U | n/a | n/a | 0.51 ± 0.045/0.13 µM | n/a | n/a | Arguello et al (2019) and Zaccara and Jaffrey (2020) |
| YTHDF2 | A/C/G U/G/C m6A G/C/U A/G/C/U | n/a | n/a | 0.79 ± 0.018/0.16 µM | n/a | n/a | Arguello et al (2019) and Zaccara and Jaffrey (2020) |
| YTHDF3 | GGm6ACU | n/a | n/a | 0.14 µM | n/a | n/a | Li et al (2017), Zaccara and Jaffrey (2020), and Zhou et al (2022) |
| IMP1 | UCGGm6ACU | n/a | n/a | 3.7 ± 0.8 nM | n/a | n/a | Nicastro et al (2023) |
| IMP1 | UCGGACU | n/a | n/a | 20.9 ± 4.0 nM | n/a | n/a | Nicastro et al (2023) |
| Erasers | Km (alpha-ketogluarate) | References | |||||
| FTO | m6A | 0.409 ± 0.023 µM | 2.88 µM | n/a | n/a | 0.296 ± 0.004 (min−1) | Jia et al (2008), Jia et al (2011), Ma et al (2012), Mauer et al (2017), Wei et al (2018), and Relier et al (2022) |
| FTO | m6Am | 1.34 µM | 2.88 µM | n/a | n/a | 8.78 (min−1) | Mauer et al (2017) |
| FTO | 3meT | 0.95 ± 0.12 µM | 2.88 µM | n/a | n/a | 0.007 ± 0.0002 (min−1) | Jia et al (2008) and Ma et al (2012) |
| FTO | 3meU | 8.51 ± 3.13 µM | 2.88 µM | n/a | n/a | 0.115 ± 0.022 (min−1) | Jia et al (2008), Jia et al (2011), and Ma et al (2012) |
| ALKBH5 | G(A/G)m6ACU | 1.38 ± 0.27 µM/192 ± 25 nM | 2.5 ± 0.5 µM | n/a | n/a | 0.169 ± 0.0106 (min−1) | Li et al (2016), Kaur et al (2022), and Peng et al (2023) |