Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by human and murine cyclin T1 requires Sp1.
P-TEFb, cyclin T1 + CDK9, is needed for the expression of cellular promoters and primate lentiviral long terminal repeats (LTRs). Curiously, cellular and lentiviral promoters differ dramatically in the requirements for positive transcriptional elongation factor (P-TEF) b activity. Lentiviral LTRs, but not cellular promoters, need an RNA-associated P-TEFb/Tat/TAR (trans-activation-responsive) RNA ternary complex. Ternary complex defective murine cycT1 is apparently inactive for lentiviral transcription. Why P-TEFb requires Tat/TAR for LTRs but not for cellular promoters remains unknown. To explore this question, we sought to determine whether DNA targeting of murine and human cyclin T1 can reconstitute a Tat/TAR-independent activity to the HIV-1 LTR. In the absence of Tat and TAR, we found that both HuCycT1 and MuCycT1 can robustly activate the HIV-1 LTR. We further showed that Sp1 is necessary and sufficient for this DNA-targeted activity. Thus, like cellular promoters, HIV-1 LTR can use P-TEFb function without a Tat/TAR RNA complex. This activity could explain recent findings of robust HIV-1 replication in rat cells that cannot form a P-TEFb/Tat/TAR moiety.
Yedavalli
Venkat S R K
VS
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.
Benkirane
Monsef
M
Jeang
Kuan-Teh
KT
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000502:physiology; D056906:Cyclin T; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D011323:Primates; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D000099253:Trans-Activation Responsive RNA-Binding Protein
D056906:Cyclin T; D016213:Cyclins; D016601:RNA-Binding Proteins; D016329:Sp1 Transcription Factor; D000099253:Trans-Activation Responsive RNA-Binding Protein; C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; C503686:Ccnt1 protein, rat