Identification of a novel posttranscriptional regulatory element by using a rev- and RRE-mutated human immunodeficiency virus type 1 DNA proviral clone as a molecular trap

Human immunodeficiency virus (HN) and all other lentiviruses utilize the es sential viral protein Rev, which binds to RRE RNA, to export their unsplice d and partially spliced mRNAs from the nucleus. We used a rev-and RRE-defec tive HIV type 1 (HIV-1) molecular clone in complementation experiments to e stablish a method for the rapid isolation of posttranscriptional regulatory elements from the mammalian genome by selecting for rescue of virus replic ation. Viruses rescued by this method contained a novel element with homolo gy to rodent intracisternal A-particle (IAP) retroelements. A functional el ement was contained within a 247-nucleotide fragment named RNA transport el ement (RTE), which was able to promote replication of the Rev- and RRE-defe ctive HIV-1 in both human lymphoid cell lines and primary lymphocytes, demo nstrating its potent posttranscriptional function. RTE was functional in ma ny cell types, indicating that the cellular factors that recognize RTE are widely expressed and evolutionarily conserved. RTE also promoted RNA export from Xenopus oocyte nuclei. RTE-mediated RNA transport was CRM1 independen t, and RTE did not show high affinity for binding to mRNA export factor TAP /NXF1, Since CRM1 and TAP/NXF1 are critical export receptors associated,vit h the two recognized mRNA export pathways, these results suggest that RTE f unctions via a distinct export mechanism. Taken together, our results ident ify a novel posttranscriptional control element that uses a conserved cellu lar export mechanism.