JBC Reviews
Recent insights into noncanonical 5′ capping and decapping of RNA

https://doi.org/10.1016/j.jbc.2022.102171Get rights and content
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The 5′ N7-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.

Keywords

RNA capping
RNA decapping
RppH
NudC
Nudt12
DXO
Rai1
ApaH

Abbreviations

ADPRC
ADP-ribosyl cyclase
APB
acryloylaminophenyl boronic acid
dpCoA
dephospho-CoA
Dxo1
decapping exonuclease
m7G
N7-methylguanosine
NAD capSeq
NAD captureSeq
NAD-capQ
NAD-cap detection and quantitation
NAD-RNA
NAD-capped RNA
NCC
noncanonical cap
Nudix
nucleotide diphosphate linked to X
PPH
pyrophosphohydrolase
ppRNA
diphosphate RNA
pRNA
monophosphate RNA
snoRNA
small nucleolar RNA
SPAAC
strain-promoted azide–alkyne cycloaddition
UDP-Glc
UDP-glucose
UDP-GlcNAc
UDP-N-acetylglucosamine
XRN
exoribonuclease

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These authors share equal first authorship.