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PMID: 12832472 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner.

Molecular and cellular biology ·Vol. 23 ·No. 14 ·2003-07-00 ·Pages 4859-69

Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O

Abstract

Positive transcription elongation factor b (P-TEFb) comprises a cyclin (T1 or T2) and a kinase, cyclin-dependent kinase 9 (CDK9), which phosphorylates the carboxyl-terminal domain of RNA polymerase II. P-TEFb is essential for transcriptional elongation in human cells. A highly specific interaction among cyclin T1, the viral protein Tat, and the transactivation response (TAR) element RNA determines the productive transcription of the human immunodeficiency virus genome. In growing HeLa cells, half of P-TEFb is kinase inactive and binds to the 7SK small nuclear RNA. We now report on a novel protein termed MAQ1 (for ménage à quatre) that is also present in this complex. Since 7SK RNA is required for MAQ1 to associate with P-TEFb, a structural role for 7SK RNA is proposed. Inhibition of transcription results in the release of both MAQ1 and 7SK RNA from P-TEFb. Thus, MAQ1 cooperates with 7SK RNA to form a novel type of CDK inhibitor. According to yeast two-hybrid analysis and immunoprecipitations from extracts of transfected cells, MAQ1 binds directly to the N-terminal cyclin homology region of cyclins T1 and T2. Since Tat also binds to this cyclin T1 N-terminal domain and since the association between 7SK RNA/MAQ1 and P-TEFb competes with the binding of Tat to cyclin T1, we speculate that the TAR RNA/Tat lentivirus system has evolved to subvert the cellular 7SK RNA/MAQ1 system.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Nucleus/genetics,metabolism Cyclin T Cyclin-Dependent Kinase 9 Cyclin-Dependent Kinases/genetics,metabolism Cyclins/genetics,metabolism Gene Products, tat/genetics,metabolism HIV Long Terminal Repeat/physiology HeLa Cells Humans Macromolecular Substances Molecular Sequence Data Positive Transcriptional Elongation Factor B Protein Serine-Threonine Kinases/genetics,metabolism Protein Subunits/metabolism RNA, Small Nuclear/metabolism RNA-Binding Proteins/genetics,metabolism Sequence Homology, Amino Acid Transcription Factors Transcription, Genetic Transfection Two-Hybrid System Techniques
Chemicals
CCNT1 protein, human CCNT2 protein, human Cyclin T Cyclins Gene Products, tat HEXIM1 protein, human Macromolecular Substances Protein Subunits RNA, Small Nuclear RNA-Binding Proteins Transcription Factors Positive Transcriptional Elongation Factor B Protein Serine-Threonine Kinases CDK9 protein, human Cyclin-Dependent Kinase 9 Cyclin-Dependent Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Michels Annemieke A
UMR 8541 CNRS, Ecole Normale Supérieure, Laboratoire de Régulation de l'Expression Génétique, 75230 Paris Cedex 05, France.
Nguyen Van Trung
Fraldi Alessandro
Labas Valérie
Edwards Mia
Bonnet François
Lania Luigi
Bensaude Olivier
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.14.4859-4869.2003
Published
2003-07-00
Pages
4859-69
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC162212
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/MCB.23.14.4859-4869.2003 PMC Full Text View journal details
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