molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

7SK is an abundant small nuclear RNA found in

metazoa Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...

ns. It plays a role in regulating transcription by controlling the positive transcription elongation factor

P-TEFb The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in ...

. 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.

Structure

An early study indicated that 7SK in cells is associated with a number of proteins and probing of the

secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

suggested a model for

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

ing 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 Protein HEXIM1 is a protein that in humans is encoded by the ''HEXIM1'' gene. Interactions HEXIM1 has been shown to interact with Cyclin T1 and Cdk9 Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. Fu ...

HEXIM2 Protein HEXIM2 is a protein that in humans is encoded by the ''HEXIM2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' ...

. 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 A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducin ...

containing protein

BRD4 Bromodomain-containing protein 4 is a protein that in humans is encoded by the ''BRD4'' gene. BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET famil ...

. 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. Detailed review.

References

External links

* * {{UCSC gene info, RN7SK Non-coding RNA