Skip to main content

The human CD3 g gene promoter is controlled by an RNA element that binds P-TEFb and is negatively regulated by HIV-1 Tat

Our studies show that HIV-1 infection provokes a progressive defect in surface TCR/CD3 receptors due to the specific and escalating loss of CD3 g mRNA. The human CD3 g gene is transcribed from a weak, lymphoid-specific promoter with significant transcription initiation site heterogeneity in normal T cells. However, early after HIV-1 infection CD3 g transcripts preferentially initiate at the +1 and +13 with further focusing over time as +1 transcripts are lost first. Mutant and deletion analysis delimited a 43 bp sequence from the +1 as critical for positive gene expression. DNA probes covering this sequence do not bind nuclear proteins. RNA probes from the +1 or +13 specifically bind the cellular proteins Cyclin T1 and cdk9 (P-TEFb) as well as HIV-1 Tat. The +1 to +43 sequence, defined as the CD3 g RCE (RNA control element), forms a secondary structure containing a uridine bulge, a side loop and a double apical loop with sequence similarity to HIV-1 TAR. Five GGCU repeats present from +18 to +37 form a similar double apical loop structure for +13 transcripts that lack the bulge and side loop. Deletion or mutation in the CD3 g RCE dramatically affects function with a 4 nt apical loop mutation abrogating both promoter activity and nuclear protein binding. Co-transfection of Tat with CD3 g promoter constructs suppresses promoter activity. In infected cells, knocking down tat gene expression restores surface TCR/CD3 whereas treatment with Tat protein accelerates TCR/CD3 downmodulation. Thus, P-TEFb binding to the CD3 g RCE in the presence of Tat is associated with negative transcriptional regulation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to KE Willard-Gallo.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Badran, B., Ravoet, M., Akl, H. et al. The human CD3 g gene promoter is controlled by an RNA element that binds P-TEFb and is negatively regulated by HIV-1 Tat. Retrovirology 3 (Suppl 1), S71 (2006). https://doi.org/10.1186/1742-4690-3-S1-S71

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1742-4690-3-S1-S71

Keywords