The Cellular Lysine Methyltransferase Set7/9-KMT7 Binds HIV-1 TAR RNA, Monomethylates the Viral Transactivator Tat, and Enhances 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: United States 18.03.2010
• Subjects: Gene Knockdown Techniques; HeLa Cells; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; HIV Long Terminal Repeat; HIV-1 - physiology; Host-Pathogen Interactions; Humans; Methylation; Positive Transcriptional Elongation Factor B - metabolism; Protein Binding; Protein Processing, Post-Translational; RNA, Viral - metabolism; tat Gene Products, Human Immunodeficiency Virus - metabolism; Transcription, Genetic
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2010.02.005

The Tat protein of HIV-1 plays an essential role in HIV gene expression by promoting efficient elongation of viral transcripts. Posttranslational modifications of Tat fine-tune interactions of Tat with cellular cofactors and TAR RNA, a stem-loop structure at the 5' ends of viral transcripts. Here, we identify the lysine methyltransferase Set7/9 (KMT7) as a coactivator 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 binds TAR RNA by itself and in complex with Tat and the positive transcription elongation factor P-TEFb. Our findings uncover a positive role for Set7/9-KMT7 and Tat methylation during early steps of the Tat transactivation cycle.