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An HIV Protein Plays a Surprising Role in Gene Activation

Retroviruses are expert manipulators when it comes to co-opting their host's cellular resources. A great deal of human complexity stems from the vast repertoire of proteins and mechanisms dedicated to the business of regulating gene expression, and retroviruses like HIV have evolved myriad ways of redirecting that machinery to their own benefit.

Humans and other eukaryotes have three types of RNA polymerases, each charged with transcribing different types of genetic elements. RNA polymerase II transcribes protein-coding genes. RNA polymerases join with so-called general transcription factors to form a pre-initiation complex (PIC) on the gene's promoter, where it binds to region rich in thymine (T) and adenine (A) named the TATA box. The first transcription factor to associate with the TATA box is called TFIID, a large protein complex containing a protein that binds the TATA box (aptly named the TATA-box-binding protein, or TBP) and several cofactors called TBP-associated factors (TAFs). PIC assembly sometimes also requires activator proteins, which can enhance transcriptional activity by supporting proper elongation of nascent transcripts.

Tat, an activator encoded in the HIV genome, is required for HIV gene activation and viral replication. It affects these processes, the current model holds, by stimulating transcript elongation and increasing RNA polymerase's processing efficiency. In a new study, Tamal Raha, Grace Cheng, and Michael Green work with human cell lines and find evidence that Tat can also stimulate PIC assembly.

While most transcription factors bind to DNA, Tat binds to an area at the end of newly emerging viral RNA called the transactivation response element (TAR). Once bound, Tat recruits a cellular complex called P-TEFb (consisting of two subunits) to the HIV promoter, and enhances RNA polymerase's transcribing capacity. Previous studies in yeast had shown that activators appear to stimulate transcription complex assembly, le
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Source:PLoS Biology


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