A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA

Cell. 1998 Feb 20;92(4):451-62. doi: 10.1016/s0092-8674(00)80939-3.

Abstract

The HIV-1 Tat protein regulates transcription elongation through binding to the viral TAR RNA stem-loop structure. We have isolated a novel 87 kDa cyclin C-related protein (cyclin T) that interacts specifically with the transactivation domain of Tat. Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor. Remarkably, the interaction of Tat with cyclin T strongly enhances the affinity and specificity of the Tat:TAR RNA interaction, and confers a requirement for sequences in the loop of TAR that are not recognized by Tat alone. Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics*
  • CHO Cells
  • Cell Nucleus / enzymology
  • Chemoreceptor Cells
  • Cloning, Molecular
  • Cricetinae
  • Cyclin C
  • Cyclin T
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics*
  • Cyclins / metabolism*
  • DNA Footprinting
  • Escherichia coli Proteins*
  • Gene Expression Regulation, Viral / physiology
  • Gene Products, tat / metabolism*
  • HIV-1*
  • Humans
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Polymerase II / metabolism
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism
  • Receptors, Cell Surface / genetics
  • Recombinant Proteins / genetics
  • Ribonucleases
  • Substrate Specificity
  • Transcription, Genetic / physiology
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Bacterial Proteins
  • CCNC protein, human
  • CCNT1 protein, human
  • Ccnc protein, mouse
  • Ccnt1 protein, mouse
  • Cyclin C
  • Cyclin T
  • Cyclins
  • Escherichia coli Proteins
  • Gene Products, tat
  • Membrane Proteins
  • RNA, Viral
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Tar protein, E coli
  • tat Gene Products, Human Immunodeficiency Virus
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • RNA Polymerase II
  • Ribonucleases

Associated data

  • GENBANK/AF045161