Guanine nucleotide depletion mediates translocation of nucleolar proteins, including RNA helicase A (DHX-9)

Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):704-11. doi: 10.1080/15257770802145132.

Abstract

DHX-9, a member of the DEXH family of RNA helicases, unwinds dsRNA/dsDNA by ATP or GTP-dependent hydrolysis. We asked whether DHX-9 played a role in the GTP depletion-induced inhibition of rRNA synthesis and/or nucleolar disruption. MPA, a specific inhibitor of inosine monophosphate dehydrogenase (IMPDH), induced a rapid translocation of DHX-9 from the nucleolus to the nucleus. EGFP-tagged DHX-9 mutated at the GTP binding site also localized to the nucleus. However, knockdown of DHX-9 by siRNA did not inhibit the rRNA synthesis or cause the nucleolar disruption. Thus, DHX-9 translocation found with IMPDH inhibition does not mediate the inhibition of rRNA synthesis.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism*
  • Dactinomycin / metabolism
  • Gene Deletion
  • Guanosine Triphosphate / metabolism*
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • IMP Dehydrogenase / metabolism
  • Mutation
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Protein Transport
  • RNA, Ribosomal / biosynthesis
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Ribosomal
  • RNA, Small Interfering
  • Recombinant Proteins
  • Dactinomycin
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • IMP Dehydrogenase
  • DHX9 protein, human
  • DEAD-box RNA Helicases