The Role of the Cellular Transcription Factor, TAF7, in HIV Biology

Division Of Basic Sciences - Nci

Investigators

Abstract

We have discovered that TAF7 is an RNA-binding protein that binds to and chaperones its target RNAs from the nucleus, delivering them to polysomes to promote protein synthesis. Our finding that TAF7 recognizes the consensus CUG trinucleotide in a bulge structure of RNA led to the prediction that TAF7 would bind to HIV TAR RNA. Indeed, we discovered that TAF7 binds directly to the TAR sequence., mutation of the TAR CUG abrogated TAF7 binding. Intriguingly, the RNA binding domain (RBD) of TAF7 is highly homologous to that of Tat and overlaps with its nuclear localization sequence (NLS). Since Tat binding to the LTR stimulates both transcription and translation of downstream genes, we will investigate if TAF7 similarly affects these processes by examining the effect of TAF7 on expression of an LTR-Luc (luciferase) construct, which contains the Luc gene under the control of the HIV-1 LTR. Additionally, we will determine whether TAF7 binding to TAR is required for regulating HIV-1 transcription.