NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.
Adaptation, Physiological
Animals
Antiviral Agents
Bone Marrow Cells
CRISPR-Cas Systems
Exonucleases
Exoribonucleases
Female
Gene Knockout Techniques
HEK293 Cells
HeLa Cells
Humans
Immunity, Innate
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins
Phosphoric Monoester Hydrolases
/ genetics
Polyphosphates
RNA Stability
RNA, Bacterial
RNA, Messenger
RNA, Viral
/ metabolism
Virus Replication
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 11 2021
25 11 2021
Historique:
received:
10
05
2020
accepted:
08
11
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
4
1
2022
Statut:
epublish
Résumé
While viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5'-triphosphate (PPP-) group that impairs degradation by the canonical 5'-3' degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5'-3' exonuclease XRN1. NUDT2 removes 5'-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5'-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.
Identifiants
pubmed: 34824277
doi: 10.1038/s41467-021-27239-y
pii: 10.1038/s41467-021-27239-y
pmc: PMC8616924
doi:
Substances chimiques
Antiviral Agents
0
Microtubule-Associated Proteins
0
Polyphosphates
0
RNA, Bacterial
0
RNA, Messenger
0
RNA, Viral
0
Exonucleases
EC 3.1.-
Exoribonucleases
EC 3.1.-
XRN1 protein, human
EC 3.1.13.1
Phosphoric Monoester Hydrolases
EC 3.1.3.2
NUDT2 protein, human
EC 3.6.1.17
triphosphoric acid
NU43IAG5BC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6918Informations de copyright
© 2021. The Author(s).
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