Recent insights into noncanonical 50 capping and decapping of RNA

The 5 ' N-7-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.

Automated summary

The 5' N-7-methylguanosine cap is a critical modification for mRNAs and other RNAs in eukaryotic cells. Recent studies have revealed a surveillance mechanism for RNA capping quality, where specific enzymes remove incomplete caps, resulting in RNA degradation. It has also been discovered that noncanonical caps derived from metabolites and cofactors can affect RNA stability and function. Enzymes and hydrolases are capable of removing these noncanonical caps, facilitating RNA degradation.