RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Table 1 Effects of m⁶A on RNA metabolism

Reader or executor	Cellular localization	Effects on m⁶A RNA	References
YTHDC1	Nucleus	Mediates the splicing and export of methylated mRNAs	[25, 26]
YTHDC2	Cytosol	Regulates mRNA degradation and translation initiation	[32]
YTHDF1	Cytosol	Interacts with initiation factors for facilitating translation initiation of m⁶A-modified mRNAs	[33]
YTHDF2	Cytosol	Promotes the degradation of methylated mRNAs by targeting to P-bodies and recruiting the CCR4–NOT complex	[27, 28]
YTHDF3	Cytosol	Promotes translation in synergy with YTHDF1, and mRNA decay in synergy with YTHDF2	[30, 34]
METTL3	Cytosol	Binds to a few m⁶A mRNAs and promotes translation initiation by mRNA looping	[35, 36]
HNRNPC, HNRNPG	Nucleus	Mediate mRNA splicing	[22,23,24]
HNRNPA2B1	Nucleus	Regulates m⁶A-dependent microRNA processes and alternative splicing	[12]
IGF2BP1/2/3	Nucleus and cytosol	Protect target mRNAs from degradation in the P-body	[31]
eIF3	Cytosol	Binds to m⁶A sites in the 5′UTRs of mRNAs and promotes cap-independent translation	[37]
HuR	Nucleus and cytosol	Binds to demethylated RNAs and increases RNA stability	[29]

YTHDC1/2 YTH domain-containing protein ½, YTHDF1/2/3 YTH domain-containing family protein 1/2/3, eIF3 Eukaryotic translation initiation factor 3, METTL3 Methyltransferase-like protein 3, HNRNPC Heterogeneous nuclear ribonucleoproteins C1/C2, HNRNPG Heterogeneous nuclear ribonucleoprotein G, HNRNPA2B1 Heterogeneous nuclear ribonucleoprotein A2B1, IGF2BP1/2/3 Insulin-like growth factor 2 mRNA binding protein 1/2/3, HuR Human antigen R

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