A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA.
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.
Wei
P
P
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037-1099, USA.
Garber
M E
ME
Fang
S M
SM
Fischer
W H
WH
Jones
K A
KA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D016466:CHO Cells; D002467:Cell Nucleus / Q000201:enzymology; D002628:Chemoreceptor Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D056745:Cyclin C; D056906:Cyclin T; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism*; D018983:DNA Footprinting; D029968:Escherichia coli Proteins; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D012260:Ribonucleases; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D001426:Bacterial Proteins; C503674:CCNC protein, human; C503684:CCNT1 protein, human; C503675:Ccnc protein, mouse; C503685:Ccnt1 protein, mouse; D056745:Cyclin C; D056906:Cyclin T; D016213:Cyclins; D029968:Escherichia coli Proteins; D015696:Gene Products, tat; D008565:Membrane Proteins; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C057331:Tar protein, E coli; D054322:tat Gene Products, Human Immunodeficiency Virus; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D012260:Ribonucleases