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NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.

ABSTRACT: 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.

SUBMITTER: Laudenbach BT

PROVIDER: S-EPMC8616924 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.

Laudenbach Beatrice T BT Krey Karsten K Emslander Quirin Q Andersen Line Lykke LL Reim Alexander A Scaturro Pietro P Mundigl Sarah S Dächert Christopher C Manske Katrin K Moser Markus M Ludwig Janos J Wohlleber Dirk D Kröger Andrea A Binder Marco M Pichlmair Andreas A

Nature communications 20211125 1

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 man ...[more]

PMID: 34824277

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NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.

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NUDT2 initiates viral RNA degradation by removal of 5'-phosphates.

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