- Ali, Ibraheem;
- Ramage, Holly;
- Boehm, Daniela;
- Dirk, Lynnette MA;
- Sakane, Naoki;
- Hanada, Kazuki;
- Pagans, Sara;
- Kaehlcke, Katrin;
- Aull, Katherine;
- Weinberger, Leor;
- Trievel, Raymond;
- Schnoelzer, Martina;
- Kamada, Masafumi;
- Houtz, Robert;
- Ott, Melanie
The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity of wild type (WT) Tat but not a Tat K71R mutant. These findings underscore the role of KMT7 as an important monomethyltransferase regulating HIV transcription through Tat.