Effect of transcription inhibition and generation of suppressive viral non-coding RNAs.

摘要: HIV-1 patients receiving combination antiretroviral therapy (cART) survive infection but require life-long adherence at high expense. In chronic cART-treated with undetectable viral titers, cell-associated RNA is still detectable, pointing to low-level transcriptional leakiness. To date, there are no FDA-approved drugs against transcription. We have previously shown that F07#13, a third generation Tat peptide mimetic competitive activity Cdk9/T1-Tat binding sites, inhibits transcription in vitro and vivo. Here, we demonstrate increasing concentrations of F07#13 (0.01, 0.1, 1 µM) cause decrease levels dose-dependent manner by inhibiting the complex formation subsequent ubiquitin-mediated sequestration degradation. Our data indicate complexes I IV contain distinct patterns ubiquitinated inhibition induced causes an overall reduction levels. This may be triggered ultimately mediated TAR-gag RNAs bind suppressive factors (similar 7SK, NRON, HOTAIR, Xist lncRNAs) enhance gene silencing latency. These PRC2, Sin3A, Cul4B, resulting epigenetic modifications. Finally, observed F07#13-mediated burden targeting R region long terminal repeat (HIV-1 promoter region, LTR), promoting both paused polymerases increased efficiency CRISPR/Cas9 editing infected cells. implies best performed under repressed state. Collectively, our results which can terminate Polymerase II generate scaffold RNAs, assemble into specific sets “RNA Machines” contribute regulation. It remains seen whether these effects also various clades varying strength, mutant LTRs, patient samples.