HIV-1 Tat Assembles a Multifunctional Transcription Elongation Complex and Stably Associates with the 7SK snRNP

• Published in: Molecular cell Vol. 38; no. 3; pp. 439 - 451
• Main Authors: Sobhian, Bijan, Laguette, Nadine, Yatim, Ahmad, Nakamura, Mirai, Levy, Yves, Kiernan, Rosemary, Benkirane, Monsef
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-05-2010; Cell Press
• Subjects: Binding Sites; Cell Line; Cell Nucleus - metabolism; Cyclin-Dependent Kinase 9 - metabolism; DNA; DNA-Binding Proteins - metabolism; Genetics; HeLa Cells; Histone-Lysine N-Methyltransferase; HIV-1 - genetics; HIV-1 - metabolism; Human genetics; Humans; HUMDISEASE; Life Sciences; Multiprotein Complexes; Myeloid-Lymphoid Leukemia Protein - metabolism; Nuclear Proteins - metabolism; Oncogene Proteins, Fusion - metabolism; Positive Transcriptional Elongation Factor B - metabolism; Promoter Regions, Genetic; PROTEINS; Repressor Proteins - metabolism; Ribonucleoproteins, Small Nuclear - genetics; Ribonucleoproteins, Small Nuclear - metabolism; RNA, Viral - biosynthesis; Stress, Physiological; tat Gene Products, Human Immunodeficiency Virus - genetics; tat Gene Products, Human Immunodeficiency Virus - metabolism; Transcriptional Activation; Transcriptional Elongation Factors - metabolism; Transfection; PROTEINS; DNA; HUMDISEASE
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2010.04.012

HIV-1 transactivator Tat has greatly contributed to our understanding of transcription elongation by RNAPII. We purified HIV-1 Tat-associated factors from HeLa nuclear extract and show that Tat forms two distinct and stable complexes. Tatcom1 consists of the core active P-TEFb, MLL-fusion partners involved in leukemia (AF9, AFF4, AFF1, ENL, and ELL), and PAF1 complex. Importantly, Tatcom1 formation relies on P-TEFb while optimal CDK9 CTD-kinase activity is AF9 dependent. MLL-fusion partners and PAF1 are required for Tat transactivation. Tatcom2 is composed of CDK9, CycT1, and 7SK snRNP lacking HEXIM. Tat remodels 7SK snRNP by interacting directly with 7SK RNA, leading to the formation of a stress-resistant 7SK snRNP particle. Besides the identification of factors required for Tat transactivation and important for P-TEFb function, our data show a coordinated control of RNAPII elongation by different classes of transcription elongation factors associated in a single complex and acting at the same promoter.
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► HIV-1 Tat assembles a multifunctional transcription elongation complex ► Purification of Tat complexes reveals the identity of elongating P-TEFb ► MLL-fusion partners and the PAF1 complex are Tat-coactivators ► Tat stably associates with 7SK snRNP through direct binding to 7SK RNA