Fig. 1: TASOR destabilizes HIV-1 LTR-driven transcripts.

a HeLa HIV-1 LTR-ΔTAR-Luc cell model. HeLa HIV-1 LTR-Luc and HeLa HIV-1 LTRΔTAR-Luc cells were lysed for Luc RNA quantification (n = 3; each replicate is presented along with the mean values and the SEM. A two-sided unpaired t test was used. ****p < 0.0001). b TASOR overexpression decreases LTR-driven Luc expression. HeLa HIV-1 LTR-ΔTAR-Luc were TASOR-depleted by transient transfection of the pLenti-CRISPR-V2 and a sgRNA guide targeting the first exon of TASOR. These TASOR-depleted cells were then transfected with increasing amounts of HA-TASOR WT or HA-TASORΔPARP encoding pAS1B vectors. Luc activity was measured and proteins were analyzed by western blot 48 h post-transfection (n = 3; each independent replicate is presented along with the mean values and the SEM. A two-sided unpaired t test was used. **p = 0.0029; *p = 0.0262. c TASOR negatively impacts LTR-driven Luc transcript at a post-transcriptional step. HeLa HIV-1 LTRΔTAR-Luc were transfected for 72 h with siCtrl or siTASOR. The luciferase activity was measured and Nuclear Run On experiments were performed (n = 3, each independent replicate is presented along with the mean values and the SEM). d HIV-2 Vpx mimics siRNA-mediated TASOR silencing in increasing LTR-driven transcript stability. Nuclear Run On performed in HeLa HIV-1 LTRΔTAR-Luc after 48 h of pAS1B-HA, pAS1B-HA-Vpx WT or R42A HIV-2 Ghana, and pAS1B-HA-Vpr HIV-1 transfection. The HIV-1 LTR-driven luciferase RNA expression was measured by RT-qPCR (n = 4, each independent replicate is presented along with the mean values and the SEM) and a western blot analysis monitored the levels of expression of the lentiviral proteins, TASOR, and HLTF (as an HIV-1 Vpr target⁷⁴). Source data are provided as a Source data file.