Guanine nucleotide depletion mediates translocation of nucleolar proteins, including RNA helicase A (DHX-9).
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.
Huang
Min
M
Department of Medicine, Division of Oncology, Stanford Cancer Center, Stanford University, Stanford, California 94305-5796, USA.
Mitchell
Beverly S
BS
D000255:Adenosine Triphosphate / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D003609:Dactinomycin / Q000378:metabolism; D017353:Gene Deletion; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport; D012335:RNA, Ribosomal / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D003609:Dactinomycin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D007168:IMP Dehydrogenase; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases