The Cellular Lysine Methyltransferase Set7/9-KMT7 Binds HIV-1 TAR RNA, Monomethylates the Viral Transactivator Tat, and Enhances HIV Transcription

• DOI: 10.1016/j.chom.2010.02.005
• Publication Date: 2010-03-18T08:34:54Z
• Authors: Sara Pagans; Steven E. Kauder; Katrin Kaehlcke; Naoki Sakane; Sebastian Schroeder; Wilma Dormeyer; Raymond C. Trievel; Eric Verdin; Martina Schnolzer; Melanie Ott
• Keywords: Cancer Research; MICROBIO; Transcription, Genetic; Histone-Lysine N-Methyltransferase; Methylation; 3. Good health; Immunology and Microbiology(all); Gene Knockdown Techniques; Host-Pathogen Interactions; HIV-1; RNA; Humans; RNA, Viral; Positive Transcriptional Elongation Factor B; tat Gene Products, Human Immunodeficiency Virus; Molecular Biology; Protein Processing, Post-Translational; HIV Long Terminal Repeat; HeLa Cells; Protein Binding

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.