7SK RNA

Structure

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. 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. 7SK associates with and inhibits the cyclin dependent kinase activity of P-TEFb through the action of the RNA binding proteins HEXIM1 or HEXIM2. 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. A La-related protein LARP7 is also found associated with 7SK, presumably in part through its interaction with the 3' end of the RNA. 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

The major function of the 7SK snRNP is control of the P-TEFb, a factor that regulates the elongation phase of transcription. 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. 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.

References

References

1. (2009). "7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor". RNA Biology.
2. (2012). "7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription". Wiley Interdisciplinary Reviews. RNA.
3. (July 1991). "Structural analyses of the 7SK ribonucleoprotein (RNP), the most abundant human small RNP of unknown function". Molecular and Cellular Biology.
4. (November 2001). "7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes". Nature.
5. (November 2001). "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription". Nature.
6. (July 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Molecular and Cellular Biology.
7. (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA". Molecular Cell.
8. (April 2005). "HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK". The Journal of Biological Chemistry.
9. (April 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". The Journal of Biological Chemistry.
10. (July 2007). "Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme". Molecular Cell.
11. (April 2008). "LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated". Nucleic Acids Research.
12. (June 2008). "The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes". EMBO Reports.
13. (March 2008). "A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis". Molecular Cell.
14. (September 2016). "Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb". Nucleic Acids Research.
15. (August 2010). "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.
16. (July 2012). "The Drosophila 7SK snRNP and the essential role of dHEXIM in development". Nucleic Acids Research.