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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.
AuthorsPaul Lawrence, Joseph S Conderino, Elizabeth Rieder
JournalVirology (Virology) Vol. 452-453 Pg. 1-11 (Mar 2014) ISSN: 1096-0341 [Electronic] United States
PMID24606677 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightPublished by Elsevier Inc.
Chemical References
  • Jumonji Domain-Containing Histone Demethylases
  • RNA Helicases
Topics
  • Animals
  • Cattle
  • Cattle Diseases (enzymology, genetics, virology)
  • Cell Line
  • Cell Nucleus (enzymology, genetics)
  • Cricetinae
  • Cytoplasm (enzymology, genetics)
  • Foot-and-Mouth Disease (enzymology, genetics, metabolism, virology)
  • Foot-and-Mouth Disease Virus (genetics, physiology)
  • Jumonji Domain-Containing Histone Demethylases (genetics, metabolism)
  • Methylation
  • Protein Binding
  • Protein Transport
  • RNA Helicases (genetics, metabolism)

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