title: A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity.
abstract: Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host-pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein--its binding partner within replication complexes--leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity.
authors: Laboratoire de Virologie Moléculaire, CNRS-Univ Paris Diderot, Institut Jacques Monod, Cell Biology Department, UMR 7592, Paris, France.
authors: Mélanie
authors: M
authors: Chenon
authors: Laurent
authors: L
authors: Camborde
authors: Soizic
authors: S
authors: Cheminant
authors: Isabelle
authors: I
authors: Jupin
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D017806:Tymovirus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D025801:Ubiquitin / Q000378:metabolism*; D014774:Virulence
chemical_list: D012367:RNA, Viral; D025801:Ubiquitin; D012324:RNA-Dependent RNA Polymerase