HIV-1 Tat Protein Increases Transcriptional Initiation and Stabilizes Elongation

Cell. 1989 Oct 20;59(2):283-92. doi: 10.1016/0092-8674(89)90290-0.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus Early Proteins
  • Adenoviruses, Human / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Directed RNA Polymerases / metabolism
  • Gene Expression
  • Gene Products, tat / metabolism*
  • Genes, Viral
  • HIV-1 / genetics*
  • HeLa Cells / metabolism
  • Humans
  • Models, Genetic
  • Mutation
  • Oncogene Proteins, Viral / metabolism
  • Plasmids
  • RNA, Viral / genetics
  • Restriction Mapping
  • Trans-Activators / metabolism*
  • Transcription, Genetic*
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Adenovirus Early Proteins
  • DNA-Binding Proteins
  • Gene Products, tat
  • Oncogene Proteins, Viral
  • RNA, Viral
  • Trans-Activators
  • tat Gene Products, Human Immunodeficiency Virus
  • DNA-Directed RNA Polymerases