Abstract
Nucleobase modifications are prevalent in eukaryotic mRNA and their discovery has resulted in the emergence of epitranscriptomics as a research field. The most abundant internal (non-cap) mRNA modification is N6-methyladenosine (m6A), the study of which has revolutionized our understanding of post-transcriptional gene regulation. In addition, numerous other mRNA modifications are gaining great attention because of their major roles in RNA metabolism, immunity, development and disease. In this Review, we focus on the regulation and function of non-m6A modifications in eukaryotic mRNA, including pseudouridine (Ψ), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), inosine, 5-methylcytidine (m5C), N4-acetylcytidine (ac4C), 2′-O-methylated nucleotide (Nm) and internal N7-methylguanosine (m7G). We highlight their regulation, distribution, stoichiometry and known roles in mRNA metabolism, such as mRNA stability, translation, splicing and export. We also discuss their biological consequences in physiological and pathological processes. In addition, we cover research techniques to further study the non-m6A mRNA modifications and discuss their potential future applications.
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Acknowledgements
This work was supported by the Ministry of Science and Technology of China (2019YFA0110902 and 2019YFA0802201 to C.Y.) and the National Natural Science Foundation of China (21825701 to C.Y.).
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Sun, H., Li, K., Liu, C. et al. Regulation and functions of non-m6A mRNA modifications. Nat Rev Mol Cell Biol 24, 714–731 (2023). https://doi.org/10.1038/s41580-023-00622-x
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DOI: https://doi.org/10.1038/s41580-023-00622-x
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