HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation.
We studied regulation of human immunodeficiency virus-1 (HIV-1) transcription by Tat and, for comparative purposes, by the adenovirus E1A protein. These two trans-activators exerted different effects. Two classes of HIV-1-promoted cytoplasmic RNA were detected, one class corresponding to full-length transcripts and the other to transcripts ending 55 and 59 nucleotides from the transcription start. Tat increased the level of the full-length class only, whereas E1A increased the levels of both classes of RNA. We also measured the effects of Tat and E1A on RNA synthesis rates. Without trans-activators, HIV-1-directed transcription was relatively weak and exhibited a marked polarity. Both Tat and E1A dramatically increased promoter-proximal transcription, while only Tat suppressed transcriptional polarity. Mutations in the TAR element did not influence basal transcription rates or the response to E1A, but eliminated trans-activation by Tat. We propose that Tat acts through TAR to increase initiation complex formation on the HIV-1 promoter and to stabilize complexes during elongation.
Laspia
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MF
Cold Spring Harbor Laboratory, New York 11724.
Rice
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AP
Mathews
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MB
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015870:Gene Expression; D015696:Gene Products, tat / Q000378:metabolism*; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010957:Plasmids; D012367:RNA, Viral / Q000235:genetics; D015183:Restriction Mapping; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; D012321:DNA-Directed RNA Polymerases