Set7/9 (KMT7) binds HIV-1 TAR RNA, monomethylates Tat and enhances Tat-dependent HIV transcription

• Published in: Cell host & microbe Vol. 7; no. 3; pp. 234 - 244
• Main Authors: Pagans, Sara, Kauder, Steven E., Kaehlcke, Katrin, Sakane, Naoki, Schroeder, Sebastian, Dormeyer, Wilma, Trievel, Raymond C., Verdin, Eric, Schnolzer, Martina, Ott, Melanie
• Format: Journal Article
• Language: English
• Published: 18.03.2010
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2010.02.005

Posttranslational modifications of the HIV-1 Tat protein have emerged as critical regulatory mechanisms that fine-tune interactions of the viral transactivator with TAR RNA and cellular cofactors. Here, we identify the lysine methyltransferase Set7/9 (renamed KMT7) as a novel co-activator of HIV transcription. Set7/9-KMT7 associates with the HIV promoter in vivo and monomethylates lysine 51, a highly conserved residue located in the RNA-binding domain of Tat. Knockdown of Set7/9-KMT7 suppresses Tat transactivation of the HIV promoter, but does not affect the transcriptional activity of methylation-deficient Tat (K51A). Set7/9-KMT7 itself binds TAR RNA and forms a complex with Tat and the positive transcription elongation factor P-TEFb. Our findings uncover novel RNA-binding properties of Set7/9-KMT7 and demonstrate a positive role of Tat methylation in early steps of the Tat transactivation cycle.