7SK RNA | |
---|---|
Identifiers | |
Symbol | 7SK |
Rfam | RF00100 |
Other data | |
RNA type | Gene |
Domain(s) | Eukaryota |
SO | SO:0000274 |
PDB structures | PDBe |
RN7SK | |
---|---|
Identifiers | |
Symbol | RN7SK |
NCBI gene | 125050 |
Other data | |
Locus | Chr. 6 p12.2 |
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.
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.[14]
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.[15] 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.[16] Detailed review.[14]