7SK RNA
7SK RNA, also known as K7 RNA, is a highly abundant, non-coding RNA molecule found in the nucleus of vertebrate cells. It plays a critical role in regulating the activity of positive transcription elongation factor b (P-TEFb), a kinase complex essential for the efficient transcription of many protein-coding genes, particularly those involved in cell growth and differentiation.
7SK RNA acts as a scaffold, binding to both P-TEFb and inhibitory proteins such as hexamethylene bisacetamide-inducible protein 1 and 2 (HEXIM1/2) or the larger complex known as the 7SK snRNP. This interaction inhibits the kinase activity of P-TEFb, effectively sequestering it and preventing premature or inappropriate gene transcription.
The balance between the active and inactive forms of P-TEFb, mediated by 7SK RNA, is highly regulated and responsive to cellular signals. Stress stimuli, such as UV irradiation or transcriptional inhibitors, can disrupt the 7SK snRNP, releasing active P-TEFb to stimulate transcription of stress-response genes.
Specific proteins and modifications to 7SK RNA itself also contribute to its regulatory role. La-related protein 7 (LARP7) binds to 7SK RNA and stabilizes it, preventing its degradation. Furthermore, modifications such as methylation can influence the interaction of 7SK RNA with other proteins and its overall function.
Understanding the complex interactions and regulatory mechanisms surrounding 7SK RNA is crucial for deciphering the intricate control of gene expression and its impact on various cellular processes and disease states. Dysregulation of the 7SK RNA/P-TEFb pathway has been implicated in conditions such as cancer and HIV infection.