[HTML][HTML] Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function

VSRK Yedavalli, C Neuveut, Y Chi, L Kleiman… - Cell, 2004 - cell.com
VSRK Yedavalli, C Neuveut, Y Chi, L Kleiman, KT Jeang
Cell, 2004cell.com
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 …
Abstract
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.
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