7SK RNA

Figure 1. Reversible association of P-TEFb with the 7SK snRNP. P-TEFb is released from the 7SK snRNP by Brd4 or HIV Tat. HEXIM is ejected and the two proteins are replaced by hrRNPs. The reverse of this process requires other unknown factors.
7SK RNA
Predicted secondary structure and sequence conservation of 7SK
Identifiers
Symbol 7SK
Rfam RF00100
Other data
RNA type Gene
Domain(s) Eukaryota
SO 0000274
RNA, 7SK small nuclear
Identifiers
Symbols RN7SK ; 7SK
External IDs OMIM: 606515 GeneCards: RN7SK Gene
Orthologs
Species Human Mouse
Entrez 125050 n/a
Ensembl ENSG00000202198 n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) Chr 6:
53 – 53 Mb		 n/a
PubMed search n/a

In molecular biology 7SK is an abundant small nuclear RNA found in metazoans.[1] It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb.[2] 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.

Composition of the 7SK snRNP

An early study indicated that 7SK in cells is associated with a number of proteins and probing of the secondary structure suggested a model for base pairing between different regions of the RNA.[3] A breakthrough in the function of the 7SK snRNP came with the finding that the positive transcription elongation factor P-TEFb was a component of the complex.[4][5] 7SK associates with and inhibits the cyclin dependent kinase activity of P-TEFb through the action of the RNA binding proteins HEXIM1[6][7] or HEXIM2.[8][9] The gamma phosphate at the 5' end of 7SK is methylated by the methylphosphate capping enzyme MEPCE which is a constitutive component of the 7SK snRNP.[10] A La related protein LARP7 is also found associated with 7SK, presumably in part through its interaction with the 3' end of the RNA.[11][12][13] Reduction of either MEPCE or LARP7 by siRNA mediated knockdown leads to destabilization of 7SK in vivo. A subset of 7SK snRNPs lack P-TEFb and HEXIM, but contains hnRNPs instead.

Function of the 7SK snRNP

The major function of the 7SK snRNP is control of the P-TEFb, a factor that regulates the elongation phase of transcription.[2] The kinase activity of P-TEFb is inhibited when the factor is in the 7SK snRNP. P-TEFb can be released from the 7SK snRNP by either the HIV transactivator Tat or the bromodomain containing protein BRD4. This release leads to a conformational change in 7SK RNA and the ejection of HEXIM.[14] hnRNPs stabilize the complex lacking P-TEFb and HEXIM. After P-TEFb functions on specific genes it is re-sequestered in the 7SK snRNP by an unknown mechanism. The 7SK snRNP has been characterized in both human and Drosophila.[15]

References

  1. ↑ Diribarne, G; Bensaude O (2009). "7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor". RNA Biol. 2 (2): 122–8. PMID 19246988.
  2. 1 2 Peterlin, BM; Brogie JE; Price DH. (2012). "7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription". Wiley Interdiscip Rev RNA 1 (1): 92–103. doi:10.1002/wrna.106. PMC 3223291. PMID 21853533.
  3. ↑ wassarman, DA; Steitz, JA (1991). "Structural analyses of the 7SK ribonucleoprotein (RNP), the most abundant human small RNP of unknown function". Mol. Cell. Biol. 7 (7): 3432–45. doi:10.1128/MCB.11.7.3432. PMC 361072. PMID 1646389.
  4. ↑ Nguyen, VT; Kiss T; Michels AA; Bensaude O (2001). "7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes". Nature 414 (6861): 322–5. doi:10.1038/35104581. PMID 11713533.
  5. ↑ Yang, Z; Zhu Q; Luo K; Zhou Q (2001). "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription". Nature 414 (6861): 317–22. doi:10.1038/35104575. PMID 11713532.
  6. ↑ Michels, AA; Nguyen VT; Fraldi A; Labas V; Edwards M; Bonnet F; Lania L; Bensaude O (2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 14 (14): 4859–69. doi:10.1128/MCB.23.14.4859-4869.2003. PMC 162212. PMID 12832472.
  7. ↑ Yik, JH; Chen R; Nishimura R; Jennings JL; Link AJ; Zhou Q (2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA". Mol. Cell 4 (4): 971–82. doi:10.1016/S1097-2765(03)00388-5. PMID 14580347.
  8. ↑ Byers, SA; Price JP; Cooper JJ; Li Q; Price DH (2005). "HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK". J. Biol. Chem. 280 (16): 16360–7. doi:10.1074/jbc.M500424200. PMID 15713662.
  9. ↑ Yik, JH; Chen R; Pezda AC; Zhou Q (2005). "Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription". J. Biol. Chem. 280 (16): 16368–76. doi:10.1074/jbc.M500912200. PMID 15713661.
  10. ↑ Jeronimo, C; Forget, D; Bouchard, A; Li, Q; Chua, G; Poitras, C; Thérien, C; Bergeron, D; Bourassa, S; Greenblatt, J; Chabot, B; Poirier, GG; Hughes, TR; Blanchette, M; Price, DH; Coulombe, B (2007). "Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme". Mol. Cell 2 (2): 262–74. doi:10.1016/j.molcel.2007.06.027. PMID 17643375.
  11. ↑ Krueger, BJ; Jeronimo, C; Roy, BB; Bouchard, A; Barrandon, C; Byers, SA; Searcey, CE; Cooper, JJ; Bensaude, O; Cohen, EA; Coulombe, B; Price, DH (2008). "LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated". Nucleic Acids Research 7 (7): 2219–29. doi:10.1093/nar/gkn061. PMC 2367717. PMID 18281698.
  12. ↑ Markert, A; Grimm M; Martinez J; Wiesner J; Meyerhans A; Meyuhas O; Sickmann A; Fischer U. (2008). "The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes". EMBO Rep. 6 (6): 569–75. doi:10.1038/embor.2008.72. PMC 2427381. PMID 18483487.
  13. ↑ He, N; Jahchan NS; Hong E; Li Q; Bayfield MA; Maraia RJ; Luo K; Zhou Q (2008). "A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis". Mol. Cell 29 (5): 588–599. doi:10.1016/j.molcel.2008.01.003. PMID 18249148.
  14. ↑ Krueger, BJ; Varzavand K; Cooper JJ; Price DH. (2010). Blagosklonny, Mikhail V., ed. "The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK". PLoS ONE 8 (8): e12335. doi:10.1371/journal.pone.0012335. PMC 2925947. PMID 20808803.
  15. ↑ Nguyen, D; Krueger, BJ; Sedore, SC; Brogie, JE; Rogers, JT; Rajendra, TK; Saunders, A; Matera, AG; Lis, JT; Uguen, P; Price, DH (2012). "The Drosophila 7SK snRNP and the essential role of dHEXIM in development". Nucleic Acids Research 40 (12): 5283–97. doi:10.1093/nar/gks191. PMC 3384314. PMID 22379134.
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