Publication of IMPRS-LS student Beatrice Laudenbach

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.