HMGA1 directly interacts with TAR to modulate basal and Tat-dependent HIV transcription

Abstract

The transactivating response element (TAR) of human immunodeficiency virus 1 (hIV-1) is essential for promoter transactivation by the viral transactivator of transcription (Tat). The Tat-TAR interaction thereby recruits active positive transcription elongation factor b (p-TeFb) from its inactive, 7sK/heXIM1-bound form, leading to efficient viral transcription. here, we show that the 7sK RNA-associating chromatin regulator hMGA1 can specifically bind to the hIV-1 TAR element and that 7sK RNA can thereby compete with TAR. The hMGA1-binding interface of TAR is located within the binding site for Tat and other cellular activators, and we further provide evidence for competition between hMGA1 and Tat for TAR-binding. hMGA1 negatively influences the expression of a hIV-1 promoter-driven reporter in a TAR-dependent manner, both in the presence and in the absence of Tat. The overexpression of the hMGA1-binding substructure of 7sK RNA results in a TAR-dependent gain of hIV-1 promoter activity similar to the effect of the shRNA-mediated knockdown of hMGA1. Our results support a model in which the hMGA1/TAR interaction prevents the binding of transcription-activating cellular co-factors and Tat, subsequently leading to reduced hIV-1 transcription. © 2013 Landes Bioscience.