Retroviral RNA elements integrate components of post-transcriptional gene expression

Retroviruses vary widely in their ability to cause neoplastic transformatio n or immunodeficiency, and may even lack pathogenicity, but all retroviruse s require cytoplasmic expression of intron-containing mRNA. In the cytoplas m, the primary viral transcript has two essential roles as mRNA template fo r protein synthesis and as genomic RNA for packaging into progeny virions. Cellular proteins are used by the virus to modulate synthesis, processing, and translation of the viral RNA. To subvert the normal RNA processing casc ade and achieve nuclear export of intron-containing viral RNA, retroviruses utilize structured RNA elements and viral or cellular protein partners. Th ese nuclear interactions determine the cytoplasmic fate of viral RNAs by fa cilitating RNA stability, nuclear export, translational efficiency, and eve n assembly of progeny virions. The HIV Rev responsive element (RRE) and Rev protein have been a informative paradigm for dissection of the process of eukaryotic RNA nuclear export. Rev is an adapter protein that bridges RRE-c ontaining RNA and the CRM I nuclear export receptor, which delivers intron- containing RNA to a nuclear export pathway typically used for 5s rRNA and p rotein transport. This review summarizes data indicating that Rev/RRE also targets cytoplasmic transcripts to the cytoskeletal polysomes and activates their translational efficiency. The interesting parallel is discussed that genetically simpler retroviruses lack a Rev-like protein and recruit cellu lar proteins to distinct RNA elements that modulate post-transcriptional ge ne expression through different export pathways. These pathways include the global mRNA export pathway mediated by Tap, and Tap- and CRM1-independent pathways. The CRM1-independent nuclear export pathway accessed by the splee n necrosis virus post-transcriptional control element is functionally linke d to RU5-mediated translational enhancement in the cytoplasm. The simple re troviral post-transcriptional control elements also modulate RNA splicing e fficiency, stability, assembly of virions, and subsequent viral egress from the cell. Thus, multiple layers of post-transcriptional control are execut ed by these retroviral RNA elements, which serve as a compact platform for interaction with nuclear and possibly cytoplasmic protein partners. Further characterization of the cellular partners and their regulation will be an important step to full understanding of nuclear-cytoplasmic connections tha t hardwire post-transcriptional gene expression in eukaryotic cells. (C) 20 01 Elsevier Science Inc. All rights reserved.