Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function.
A single transcript in its unspliced and spliced forms directs the synthesis of all HIV-1 proteins. Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts. Previously, CRM1 was identified as a cellular cofactor for Rev-dependent export of intron-containing HIV-1 RNA. Here, we present evidence that Rev/CRM1 activity utilizes the ATP-dependent DEAD box RNA helicase, DDX3. We show that DDX3 is a nucleo-cytoplasmic shuttling protein, which binds CRM1 and localizes to nuclear membrane pores. Knockdown of DDX3 using either antisense vector or dominant-negative mutants suppressed Rev-RRE-function in the export of incompletely spliced HIV-1 RNAs. Plausibly, DDX3 is the human RNA helicase which functions in the CRM1 RNA export pathway analogously to the postulated role for Dbp5p in yeast mRNA export.
Yedavalli
Venkat S R K
VS
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Neuveut
Christine
C
Chi
Ya-Hui
YH
Kleiman
Lawrence
L
Jeang
Kuan-Teh
KT
D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D015752:Genes, env / Q000502:physiology*; D015658:HIV Infections / Q000201:enzymology / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology; D000097606:Exportin 1 Protein
D053487:DEAD-box RNA Helicases; D028884:Karyopherins; D020365:RNA Helicases; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C119332:DDX3X protein, human