title: Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of Jumonji C-domain containing protein 6 in RHA demethylation.
abstract: Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication.
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, NAA, Plum Island Animal Disease Center, PO Box 848, Greenport, NY 11944-0848, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, NAA, Plum Island Animal Disease Center, PO Box 848, Greenport, NY 11944-0848, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Conderino
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, NAA, Plum Island Animal Disease Center, PO Box 848, Greenport, NY 11944-0848, USA. Electronic address: elizabeth.rieder@ars.usda.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D006224:Cricetinae; D003593:Cytoplasm / Q000201:enzymology / Q000235:genetics; D005536:Foot-and-Mouth Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D011485:Protein Binding; D021381:Protein Transport; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; D020365:RNA Helicases
keywords: Arginine demethylation; Foot-and-mouth disease virus (FMDV); Jumonji C-domain containing protein 6 (JMJD6); RNA helicase A (RHA)