Department of Biological Sciences, Columbia University, New York, New York, USA.
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
J Biol Chem. 2022 Aug;298(8):102171. doi: 10.1016/j.jbc.2022.102171. Epub 2022 Jun 21.
The 5' N-methylguanosine cap is a critical modification for mRNAs and many other RNAs in eukaryotic cells. Recent studies have uncovered an RNA 5' capping quality surveillance mechanism, with DXO/Rai1 decapping enzymes removing incomplete caps and enabling the degradation of the RNAs, in a process we also refer to as "no-cap decay." It has also been discovered recently that RNAs in eukaryotes, bacteria, and archaea can have noncanonical caps (NCCs), which are mostly derived from metabolites and cofactors such as NAD, FAD, dephospho-CoA, UDP-glucose, UDP-N-acetylglucosamine, and dinucleotide polyphosphates. These NCCs can affect RNA stability, mitochondrial functions, and possibly mRNA translation. The DXO/Rai1 enzymes and selected Nudix (nucleotide diphosphate linked to X) hydrolases have been shown to remove NCCs from RNAs through their deNADding, deFADding, deCoAping, and related activities, permitting the degradation of the RNAs. In this review, we summarize the recent discoveries made in this exciting new area of RNA biology.
5' N-甲基鸟苷帽是真核细胞中 mRNA 和许多其他 RNA 的关键修饰。最近的研究揭示了一种 RNA 5' 加帽质量监控机制,DXO/Rai1 脱帽酶去除不完整的帽子,并使 RNA 降解,我们也将这个过程称为“无帽降解”。最近还发现,真核生物、细菌和古菌的 RNA 可以具有非典型的帽子(NCC),这些帽子主要来自代谢物和辅助因子,如 NAD、FAD、去磷酸辅酶 A、UDP-葡萄糖、UDP-N-乙酰葡萄糖胺和二核苷酸多磷酸盐。这些 NCC 可以影响 RNA 的稳定性、线粒体功能,并且可能影响 mRNA 翻译。已经表明,DXO/Rai1 酶和选定的 Nudix(核苷酸二磷酸与 X 相连)水解酶通过去 NADding、去 FADding、去 CoAping 以及相关活性从 RNA 上去除 NCC,从而允许 RNA 降解。在这篇综述中,我们总结了在这个令人兴奋的 RNA 生物学新领域取得的最新发现。