RNAPII CTD Case Study

The variations in the gene expression programs and regulation led to have phenomenal results in cellular differentiation, and adaptability of all organisms. Indeed, the dysregulation activity in transcription progression may actually cause a broad range of disease and syndromes. RNAPII CTD has emerged as an essential regulator of transcription progression. The combinatorial modification of RNAPII CTD codes may lead to innumerous possibilities to control gene expression important for.... In the last decade, numerous functions of RNAPII CTD have been identified, which demonstrated that their activities are important for cellular gene expression, cell cycle, and differentiation. It is new beginning of different regulatory mechanism impact in
2014). Another instance shows that viral infection inhibits CTD phosphorylation by a nonstructural protein (NSs) from Bunyamwera virus (BUNV), which prevents S-2 CTD phosphorylation and finally inhibits type I interferon IFN-β gene expression suggesting a block in transition from initiation to elongation in the mammalian host (Thomas et al. 2004). The influenza virus RNA-dependent RNA polymerase (vRNP) also interacts with the S-5 CTD and inhibits the RNAPII elongation (Engelhardt et al. 2005; Chan et al. 2006). Another study defines that cyclinT1/CDK9 serves as an adapter to mediate the interaction of vRNP and S-2 RNAPII CTD and promote influenza viral transcription (Zhang et al. 2010a). Several other viruses also influence the phosphorylation state of RNAPII CTD and alter the host cell transcription for example; Cytomegalovirus (Baek et al. 2004; Tamrakar et al. 2005), Epstein-Barr Virus (Bark-Jones et al. 2006; Palermo et al. 2011), Human Immunodeficiency Virus type (Isel and Karn 1999; Zhou et al. 2000; Coiras et al. 2013; Chen
Dysregulation of RNAP II CTD phosphorylation facilitates aberrant transcription profiles and may result in cancer progression and metastasis. For example, phosphorylation of the S-2 RNAPII CTD strongly increased in the invasive breast cancer cell lines, which further indicates an increase in the P-TEFb kinase activity (Ji et al. 2014). Many other cancerous cells show the relation with CTD phosphorylation such as Leukemia ((Pallis et al. 2013)), liver cancer cell lines (Bi et al. 2013) chronic lymphocytic leukemia (Walsby et al. 2014). Most of these cancerous cells are exhibited the dysregulation of enzymes that modify CTD residues, which further proceed for CTD dependent transcription irregularities. These enzymes and proteins used as a target to inhibit the CTD modification and transcription inhibition. For example, the small molecule inhibitors LDC3140 and LDC4297 inhibit CDK7, a critical S-5 and S-7 kinase, and thereby induced apoptosis (Kelso et al. 2014). The loss of CDK7 function disturbs the stability of PIC and eventually triggers decrease in S-5 phosphorylation in the CTD and loss of RNAPII from promoters. This in turn leads to effect on mRNA synthesis rates, an altered state of transcription inside cells, and cell cycle delay and finally reduced survival of tumor cells (Kelso et al. 2014). A potent CDK9 inhibitor, LY2857785