Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNA polymerase II transcripts accumulate within mammalian nuclei at distinct sites and exhibit varying morphology. Certain RNA species are organized in elongated structures, whereas others appear as dot-like concentrations. To analyze the status of the RNA within these accumulations, we investigated the composition of accumulations derived from Epstein-Barr virus (EBV) genes, human papilloma virus 18 (HPV18) open reading frames E6 and E7, as well as heat shock protein 89a (hsp89alpha) and 89beta (hsp89beta) genes. No differential distribution of exon and intron sequences within concentrations of EBV RNA could be observed. Whereas accumulations of hsp89alpha and hsp89beta always coincided with Sm antigen foci, the RNA of EBV and HPV18 never co-localized with these foci. This excludes Sm antigen foci as the only sites of splicing and suggests gene-specific variation in the nuclear localization of transcripts. Two sets of experiments were performed to assess whether transcripts in the RNA accumulations are in statu nascendi or products released from a discrete gene locus. Because RNA transcripts derived from EBV genes, which are located on both ends of the genome, were all distributed along the entire length of the RNA signals, they cannot be derived from a highly decondensed genomic DNA extending throughout elongated RNA accumulations. Furthermore, removal of labeled RNA sequences and subsequent visualization of DNA confirmed the confinement of the genomic sequences to a small subregion of the area occupied by accumulated RNA. Therefore, this study supports the view of RNA accumulations as a stream of molecules that delineate a path from a dot-like gene locus toward the nuclear envelope for export into the cytoplasm.
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PMID:Nuclear RNA accumulations contain released transcripts and exhibit specific distributions with respect to Sm antigen foci. 936 24

A role for human papilloma virus (HPV) infection in the pathogenesis of head and neck neoplasms has gained support in recent years. Expression of two early-region HPV genes, E6 and E7, is widely accepted as essential for viral-induced carcinomas of the genital tract. These oncoproteins interact with the products of the cellular tumor suppressor genes, p53 and retinoblastoma, and inactivate them. Examining E6/E7 transforming gene expression is an important step toward elucidating the pathogenesis of HPV in head and neck neoplasms. We introduce nasal inverted papilloma (IP) as a novel system for evaluating viral genomic expression and transforming gene regulation of tumorigenesis by virtue of its association to HPV infection and potential for malignant progression. We describe here a reverse transcriptase-polymerase chain reaction approach for the detection of HPV E6/E7-specific transcripts in RNA extracted from IR. A primer pair flanking previously mapped HPV 6 E6/E7 splice donor/acceptor sites was used to direct amplification of cDNA. Reverse transcriptase-polymerase chain reaction experiments generated products representing the 1.2 Kb E1E4 splice transcript and a smaller unclassified fragment in IP from two patients. These results provide evidence for HPV 6 E6/E7 expression in IP with the potential to encode transforming proteins.
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PMID:The HPV 6 E6/E7 transforming genes are expressed in inverted papilloma. 952 9

Hutchinson Gilford syndrome (progeria [PG]) is a human disease associated with accelerated aging. To elucidate the acceleration mechanism, we first tried to transform a PG-derived cell line by infection of a recombinant adenovirus expressing HPV (human papilloma virus)-E6 and HPV-E7 genes. The transfected PG cells had a greater number of population doublings (PD) (>80), faster doubling time, and less staining of senescence-associated ss-galactosidase than the nontransfected PG cells. The transfected cells also showed markedly more detectable telomerase activity than the nontransformed cells. The expression levels of the genes in the E6-transduced and E7-transduced cell line were then compared with those of the nontransfected cell line using an mRNA differential display method, following reverse-transcriptase polymerase chain reaction analysis. Expression of huntingtin interacting protein-1 (HIP-1) gene was found to be increased not only in PG cells but also in fibroblast cells from aged healthy donors. Thus, HIP-1 might be a molecular assistant in the pathogenesis of the cellular senescent process in the human cells tested.
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PMID:Increased expression of the Huntingtin interacting protein-1 gene in cells from Hutchinson Gilford Syndrome (Progeria) patients and aged donors. 1457 Aug 52

Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.
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PMID:E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP). 1799 Sep 4

The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt's lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.
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PMID:BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. 2250 28