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Gene Review

RN7SK  -  RNA, 7SK small nuclear

Homo sapiens

Synonyms: 7SK
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Disease relevance of RN7SK

  • The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses [1].
  • Binding of HEXIM1 is a prerequisite for association of P-TEFb with the G302-C324 apical region of the 3' hairpin of 7SK that is highly reminiscent of the human immunodeficiency virus transactivation-responsive RNA [2].
  • A major portion of nuclear P-TEFb is sequestered and inactivated by the coordinated actions of the 7SK snRNA and the HEXIM1 protein, whose induced dissociation from P-TEFb is crucial for stress-induced transcription and pathogenesis of cardiac hypertrophy [3].
  • We have isolated and characterized two recombinant lambda phages containing sequences homologous to 7SK RNA which code for a RNA 330 nucleotides long in an "in vitro" transcription system [4].

High impact information on RN7SK

  • RNA polymerase III transcription of adjacent plasmid sequences can be directed by this promoter in the complete absence of the 7SK RNA coding region, indicating that no internal promoter sequences are required [5].
  • Cdk9 was limiting for cardiac growth, shown by suppressing its inhibitor (7SK) in culture and preventing downregulation of its activator (cyclin T1) in mouse myocardium.Note: In the AOP version of this article, the numbering of the author affiliations was incorrect [6].
  • The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription [1].
  • 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D [1].
  • In those organisms, the function of P-TEFb is influenced negatively by HEXIM proteins and 7SK snRNA and positively by a variety of recruiting factors [7].

Biological context of RN7SK

  • Brd4, HEXIM1, and 7SK are all implicated in regulating cell growth, which may result from their dynamic control of the general transcription factor P-TEFb [8].
  • Since HEXIM1 expression is induced in cells treated with hexamethylene bisacetamide, a potent inducer of cell differentiation, targeting the general transcription factor P-TEFb by HEXIM1/7SK may contribute to the global control of cell growth and differentiation [9].
  • Consistently, point mutations in an evolutionarily conserved motif (aa 202-205) were found to suppress P-TEFb binding and inhibition without affecting 7SK recognition [10].
  • 7SK RNA has extensive sequence complementarity to U4 snRNA, within the U4/U6 base pairing domain, and also to U11 snRNA [11].
  • We demonstrate that two structurally and functionally distinct protein binding elements located in the 5'- and 3'-terminal hairpins of 7SK support the in vivo recruitment of HEXIM1 and P-TEFb [2].

Anatomical context of RN7SK


Associations of RN7SK with chemical compounds

  • The large complex is composed of P-TEFb, 7SK small nuclear RNA, and hexamethylene bisacetamide-inducible protein 1 (Hexim1) [16].
  • The 3'-terminal adenylic acid residue in several human small RNAs including signal recognition particle (SRP) RNA, nuclear 7SK RNA, U2 small nuclear RNA, and ribosomal 5S RNA is caused by a post-transcriptional adenylation event (Sinha, K., Gu, J., Chen, Y., and Reddy, R. (1998) J. Biol. Chem. 273, 6853-6859) [17].
  • In this study, we have used dimethyl sulphate and DNase I treatment of HeLa cells and nuclei, respectively, followed by linker-mediated polymerase chain reaction, to obtain in vivo footprints of proteins binding to the promoter of the Pol III-transcribed 7SK gene [18].
  • We describe the development of an inducible siRNA expression system that is based on the tetracycline repressor and eukaryotic RNA polymerase III promoters (U6 and 7SK) [19].

Physical interactions of RN7SK

  • It is proposed that 7SK RNA binding to a HEXIM1 multimer promotes the simultaneous recruitment and hence inactivation of multiple P-TEFb units [20].
  • Electrophoretic mobility shift assays and in vitro kinase assays demonstrate that HEXIM2 forms complexes containing 7SK and P-TEFb and, in conjunction with 7SK, inhibits P-TEFb kinase activity [21].
  • Moreover, the arginine-rich motif within it is essential for its binding to 7SK snRNA, P-TEFb, and inhibition of transcription [22].

Regulatory relationships of RN7SK

  • Deletion of the first 121 amino acids of HEXIM1 allowed it to inhibit P-TEFb partially in the absence of 7SK RNA [23].
  • Here we show that, like HEXIM1, a highly homologous protein named HEXIM2 also possesses the ability to inactivate P-TEFb to suppress transcription through a 7SK-mediated interaction with P-TEFb [24].

Other interactions of RN7SK

  • Inhibition of cellular transcription by chemical agents or ultraviolet irradiation trigger the complete disruption of the P-TEFb/7SK complex, and enhance CDK9 activity [25].
  • Inhibition of transcription results in the release of both MAQ1 and 7SK RNA from P-TEFb [12].
  • Positive transcription elongation factor b (P-TEFb) regulates eukaryotic gene expression at the level of elongation, and is itself controlled by the reversible association of 7SK RNA and an RNA-binding protein, HEXIM1 or HEXIM2 [23].
  • Consistently, a minimal regulatory RNA composed of the 5' and 3' hairpins of 7SK can modulate polymerase II transcription in HeLa cells [2].
  • The 7SK-binding motif in HEXIM1 contains clusters of positively charged residues reminiscent of the arginine-rich RNA-binding motif found in a wide variety of proteins [26].
  • Through cooperatively dephosphorylating Cdk9 in response to Ca2+ signaling, PP2B and PP1alpha alter the P-TEFb functional equilibrium through releasing P-TEFb from 7SK snRNP for transcription [27].

Analytical, diagnostic and therapeutic context of RN7SK


  1. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Yang, Z., Zhu, Q., Luo, K., Zhou, Q. Nature (2001) [Pubmed]
  2. Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding. Egloff, S., Van Herreweghe, E., Kiss, T. Mol. Cell. Biol. (2006) [Pubmed]
  3. Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA. Chen, R., Yang, Z., Zhou, Q. J. Biol. Chem. (2004) [Pubmed]
  4. A sequence upstream from the coding region is required for the transcription of the 7SK RNA genes. Murphy, S., Tripodi, M., Melli, M. Nucleic Acids Res. (1986) [Pubmed]
  5. The in vitro transcription of the 7SK RNA gene by RNA polymerase III is dependent only on the presence of an upstream promoter. Murphy, S., Di Liegro, C., Melli, M. Cell (1987) [Pubmed]
  6. Activation and function of cyclin T-Cdk9 (positive transcription elongation factor-b) in cardiac muscle-cell hypertrophy. Sano, M., Abdellatif, M., Oh, H., Xie, M., Bagella, L., Giordano, A., Michael, L.H., DeMayo, F.J., Schneider, M.D. Nat. Med. (2002) [Pubmed]
  7. Controlling the elongation phase of transcription with P-TEFb. Peterlin, B.M., Price, D.H. Mol. Cell (2006) [Pubmed]
  8. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Yang, Z., Yik, J.H., Chen, R., He, N., Jang, M.K., Ozato, K., Zhou, Q. Mol. Cell (2005) [Pubmed]
  9. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Yik, J.H., Chen, R., Nishimura, R., Jennings, J.L., Link, A.J., Zhou, Q. Mol. Cell (2003) [Pubmed]
  10. Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. Michels, A.A., Fraldi, A., Li, Q., Adamson, T.E., Bonnet, F., Nguyen, V.T., Sedore, S.C., Price, J.P., Price, D.H., Lania, L., Bensaude, O. EMBO J. (2004) [Pubmed]
  11. Structural analyses of the 7SK ribonucleoprotein (RNP), the most abundant human small RNP of unknown function. Wassarman, D.A., Steitz, J.A. Mol. Cell. Biol. (1991) [Pubmed]
  12. MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner. Michels, A.A., Nguyen, V.T., Fraldi, A., Labas, V., Edwards, M., Bonnet, F., Lania, L., Bensaude, O. Mol. Cell. Biol. (2003) [Pubmed]
  13. Increased association of 7SK snRNA with Tat cofactor P-TEFb following activation of peripheral blood lymphocytes. Haaland, R.E., Herrmann, C.H., Rice, A.P. AIDS (2003) [Pubmed]
  14. The conserved 7SK snRNA gene localizes to human chromosome 6 by homolog exclusion probing of somatic cell hybrid RNA. Driscoll, C.T., Darlington, G.J., Maraia, R.J. Nucleic Acids Res. (1994) [Pubmed]
  15. Staf, a promiscuous activator for enhanced transcription by RNA polymerases II and III. Schaub, M., Myslinski, E., Schuster, C., Krol, A., Carbon, P. EMBO J. (1997) [Pubmed]
  16. Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promoters. Kohoutek, J., Blazek, D., Peterlin, B.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Purification, characterization, and cloning of the cDNA of human signal recognition particle RNA 3'-adenylating enzyme. Perumal, K., Sinha, K., Henning, D., Reddy, R. J. Biol. Chem. (2001) [Pubmed]
  18. In vivo footprinting studies suggest a role for chromatin in transcription of the human 7SK gene. Boyd, D.C., Greger, I.H., Murphy, S. Gene (2000) [Pubmed]
  19. Inducible shRNA expression for application in a prostate cancer mouse model. Czauderna, F., Santel, A., Hinz, M., Fechtner, M., Durieux, B., Fisch, G., Leenders, F., Arnold, W., Giese, K., Klippel, A., Kaufmann, J. Nucleic Acids Res. (2003) [Pubmed]
  20. Transcription-dependent association of multiple positive transcription elongation factor units to a HEXIM multimer. Dulac, C., Michels, A.A., Fraldi, A., Bonnet, F., Nguyen, V.T., Napolitano, G., Lania, L., Bensaude, O. J. Biol. Chem. (2005) [Pubmed]
  21. HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK. Byers, S.A., Price, J.P., Cooper, J.J., Li, Q., Price, D.H. J. Biol. Chem. (2005) [Pubmed]
  22. Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. Barboric, M., Kohoutek, J., Price, J.P., Blazek, D., Price, D.H., Peterlin, B.M. EMBO J. (2005) [Pubmed]
  23. Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. Li, Q., Price, J.P., Byers, S.A., Cheng, D., Peng, J., Price, D.H. J. Biol. Chem. (2005) [Pubmed]
  24. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription. Yik, J.H., Chen, R., Pezda, A.C., Zhou, Q. J. Biol. Chem. (2005) [Pubmed]
  25. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nguyen, V.T., Kiss, T., Michels, A.A., Bensaude, O. Nature (2001) [Pubmed]
  26. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Yik, J.H., Chen, R., Pezda, A.C., Samford, C.S., Zhou, Q. Mol. Cell. Biol. (2004) [Pubmed]
  27. PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Chen, R., Liu, M., Li, H., Xue, Y., Ramey, W.N., He, N., Ai, N., Luo, H., Zhu, Y., Zhou, N., Zhou, Q. Genes Dev. (2008) [Pubmed]
  28. Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. Matera, A.G., Ward, D.C. J. Cell Biol. (1993) [Pubmed]
  29. Observations on the structure of two human 7SK pseudogenes and on homologous transcripts in vertebrate species. Humphries, P., Russell, S.E., McWilliam, P., McQuaid, S., Pearson, C., Humphries, M.M. Biochem. J. (1987) [Pubmed]
  30. Common RNA polymerase I, II, and III upstream elements in mouse 7SK gene locus revealed by the inverse polymerase chain reaction. Moon, I.S., Krause, M.O. DNA Cell Biol. (1991) [Pubmed]
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