Abstract
HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68ΔC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68ΔC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68ΔC. We demonstrate that inhibition of HIV expression by Sam68ΔC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68ΔC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.
Highlights
Expression of the full coding potential of the HIV-1 genome is dependent upon a number of post-transcriptional processes
The Rev protein is translated in the cytoplasm, shuttles into the nucleus where it multimerizes on the Rev Response Element (RRE) contained in the introns of the incompletely spliced HIV-1 mRNAs
To address this question directly, we examined the ability of Sam68ΔC to inhibit expression of HIV-1 Gag RNAs utilizing different nuclear export elements; the constitutive transport element (CTE) from Mason-Pfizer Monkey virus that interacts directly with Tap (Gag-CTE), or the RRE that requires Rev and Crm1 (Gag-RRE) (Fig. 1a) [35]
Summary
Expression of the full coding potential of the HIV-1 genome is dependent upon a number of post-transcriptional processes. Resulting HIV1 mRNAs can be grouped into three classes: the unspliced, 9 kb class, encoding Gag and GagPol; the singly spliced, 4 kb class, encoding Vif, Vpr, Vpu and Env; and the multiply spliced, 2 kb class, encoding Tat, Rev and Nef. Incompletely spliced mRNAs are normally retained in the nucleus but the virus has evolved a mechanism for the transport of the 9 kb and 4 kb viral mRNAs to the cytoplasm. The Rev protein is translated in the cytoplasm, shuttles into the nucleus where it multimerizes on the Rev Response Element (RRE) contained in the introns of the incompletely spliced HIV-1 mRNAs. Once Rev binds to the RNA, its nuclear export signal (NES) interacts with Crm and mediates export to the cytoplasm [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
