Fig. 1.

The 7SK snRNP is a reservoir of nuclear P-TEFb that can be withdrawn for activated transcription in response to HIV-1 infection, stress and other growth-stimulating signals. In the nucleus, a major portion of P-TEFb is sequestered in the 7SK snRNP, where the integrity of 7SK snRNA is maintained by MePCE and LARP7 and P-TEFb’s kinase activity is inhibited by HEXIM1 in a 7SK-dependent manner. Under a number of conditions including HIV-1 infection, certain stress treatments, exposure of cardiac myocytes to hypertrophic signals and activation of TCR in T cells, 7SK snRNP is disrupted to release P-TEFb for transactivation of P-TEFb-dependent genes. When P-TEFb is released during HIV-1 infection, it joins the viral Tat protein and several other host cellular proteins whose identification and characterization will be discussed below. Under other conditions that disrupt the 7SK snRNP, P-TEFb is picked up by Brd4 and delivered to a chromatin template to stimulate general transcriptional elongation. Contrary to those stress and growth-promoting signals, treating murine erythroleukemia cells with the differentiation-inducer HMBA shifts the P-TEFb equilibrium to the HEXIM1/7SK-bound state. A low level of 7SK snRNP has also been detected on the HIV-1 LTR under basal, un-stimulated conditions although its physiological significance is yet-to-be determined