Distinct nucleocytoplasmic export pathways utilized by retroviral mRNAs

While cellular intron-containing mRNAs are usually retained in the nucleus, the retroviral unspliced RNA must exit the nucleus since it serves as genomic RNA for progeny virions as well as mRNA encoding the Gag/pol polyprotein. The export of the unspliced viral RNA is facilitated by the presence of inefficiently used splice sites and is mediated through complex posttranscriptional control mechanisms. All lentiviruses such as HIV-1 depend on the viral Rev protein which binds to the Rev responsive element, RRE, and promotes the nuclear export and expression of intron-containing HIV-1 mRNAs. In contrast, type D retrovirus expression is mediated via a cellular protein, CTEBP, which binds to the viral CTE, an RNA element with an extended stem-loop structure. In the presence of the positive acting factors, the RRE- and CTE-containing mRNAs are efficiently transported to the cytoplasm. We demonstrated that these mRNAs utilize distinct nuclear export pathways and that the CTE pathway shares features with the cellular mRNA pathway. Recently, it has been demonstrated that the human protein hCRM1 interacts directly with the nuclear export signal of Rev. We found further that hCRM1 associates with Rev in the nucleolus of living human cells, in addition, we showed that the nucleoporin Nup98 is able to interact with Rev-hCRM1 complex and also associates with Ran GTPase. Therefore, hCRM1 acts as a physical link between Rev's nuclear export signal and the nuclear port complex.

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