Publication of IMPRS-LS student Beatrice Laudenbach

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Laudenbach, B.T., Krey, K., Emslander, Q., Andersen, L.L., Reim, A., Scaturro, P., Mundigl, S., Dächert, C., Manske, K., Moser, M., Ludwig, J., Wohlleber, D., Kröger, A., Binder, M., and Pichlmair, A.
(IMPRS-LS students are in bold)
Nat Commun, 2021, 12, 6918
DOI: 10.1038/s41467-021-27239-y

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

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.