The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription.
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.
Pagans
Sara
S
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Kauder
Steven E
SE
Kaehlcke
Katrin
K
Sakane
Naoki
N
Schroeder
Sebastian
S
Dormeyer
Wilma
W
Trievel
Raymond C
RC
Verdin
Eric
E
Schnolzer
Martina
M
Ott
Melanie
M
D055785:Gene Knockdown Techniques; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008745:Methylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012367:RNA, Viral / Q000378:metabolism*; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D011495:Histone-Lysine N-Methyltransferase; D042925:Positive Transcriptional Elongation Factor B