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The transactivator of transcription protein, commonly known as Tat, is a small, multifunctional regulatory protein encoded by the human immunodeficiency virus type 1 (HIV-1). Tat is essential for efficient viral replication and plays a pivotal role in controlling HIV gene expression at both transcriptional and post-transcriptional levels. Tat binds to an RNA stem-loop structure called the transactivation response element (TAR), located at the 5′ end of all nascent HIV transcripts. This interaction recruits cellular positive transcription elongation factor b (P-TEFb), composed mainly of CDK9 and cyclin T1. P-TEFb phosphorylates RNA polymerase II and other factors to overcome promoter-proximal pausing, allowing full-length viral mRNA synthesis. Tat can also modulate host cell gene expression and stimulate translation efficiency for certain viral mRNAs.
Binds to TAR element, recruits P-TEFb, stimulates Pol II processivity
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