Requirement of DDX3 DEAD Box RNA Helicase for HIV-1 Rev-RRE Export Function
Copyright policy )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.
- National Institutes of Health United States
- National Institute of Health Pakistan
- National Institute of Allergy and Infectious Diseases United States
- McGill University Canada
Cytoplasm, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear, HIV Infections, Exportin 1 Protein, Karyopherins, Virus Replication, Genes, env, DEAD-box RNA Helicases, HIV-1, Nuclear Pore, Humans, RNA, Viral, Amino Acid Sequence, RNA Helicases
Cytoplasm, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear, HIV Infections, Exportin 1 Protein, Karyopherins, Virus Replication, Genes, env, DEAD-box RNA Helicases, HIV-1, Nuclear Pore, Humans, RNA, Viral, Amino Acid Sequence, RNA Helicases
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