Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Form and function: The natural product myxopyronin A provides the key to understanding the inhibition of bacterial RNA polymerase and should spark new ideas for the design of new antibiotics against tuberculosis and other infectious diseases.
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PMID:Lost in transcription--inhibition of RNA polymerase. 1929 13

There has been considerable therapeutic interest in the development of human vaccines against cancers and infectious diseases such as HIV and biowarfare agents by using transfected mRNAs for antigenic proteins of interest. The highest expression levels of these proteins are obtained when the transfected mRNA contains 5'-capped ends. In the present study, the locked nucleic acid (LNA)-modified cap analogue 3, m(7(LNA))G[5']ppp[5']G, has been synthesized and its biological properties were examined. The LNA-modified cap analogue was an efficient substrate for T7 RNA polymerase, and the mRNA transcribed, with a poly(A) tail, was efficiently utilized in an in vitro translation process. The RNA with the 5'-LNA-modified cap was found to be approximately 1.61- and 1.28-fold more stable than the RNA with the 5'-standard 4 and ARCA cap, respectively, and approximately 4.23-fold more stable than the uncapped control RNA. The RNA capped with the m(7(LNA))G[5']ppp[5']G 3 cap analogue was translated the most efficiently, with approximately 3.2-fold more activity than the standard cap, m(7)G[5']ppp[5']G 4. Furthermore, we have developed a nonradioactive analytical HPLC assay to determine that the LNA-modified 3 cap analogue was incorporated solely into the forward orientation. Molecular modeling of the m(7(LNA))G[5']ppp[5']G 3 cap analogue with the cap binding protein elF4E complex indicates that the LNA-modified cap-protein complex is more stable by 47.28 kcal/mol as compared to the standard mCAP-protein complex. These findings suggest that the new antireverse cap analogue m(7(LNA))G[5']ppp[5']G 3 is a potential candidate for RNA-based therapeutic vaccine production as well as studying biochemical processes.
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PMID:Locked nucleic acid (LNA)-modified dinucleotide mRNA cap analogue: synthesis, enzymatic incorporation, and utilization. 1938 20

Chronic hepatitis B (HBV) and C virus (HCV) infection can lead to liver cirrhosis, hepatocellular carcinoma and death. Treatment of these worldwide prevalent infectious diseases is subject to intensive research efforts with development of new antiviral substances and optimization of treatment strategies using molecular markers. The goal of HBV and HCV treatment is control and elimination of viral replication, respectively, thereby preventing hepatitis-associated complications. While interferon alpha is used less frequently to treat hepatitis B today, it is still (in the pegylated or albumin-fused form) an essential component of hepatitis C therapy. The growing number of targeted therapies such as new nucleus(t)ide analogs, HCV protease and RNA polymerase inhibitors and other new compounds has added complexity to the treatment of viral hepatitis. This update summarizes the current standard of care as well as new developments in chronic hepatitis B and C therapy.
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PMID:[Viral hepatitis B und C]. 1944 16

Saliva has been suggested as an easily accessible and a noninvasive diagnostic alternative for detection of antibodies. To identify and characterize Schistosoma japonicum (S. japonicum) antigens that are recognized by saliva of infected host, we have used a pool of saliva from infected patients to immunoscreen an egg cDNA library of S. japonicum. The open reading frame of the isolated two clones encodes same protein of 116 amino acids exhibiting 100% identity to an amino acid sequence (AY222893) of S. japonicum in NCBInr database. The protein encoded is inferred a secretory protein with a molecular mass of 13 kDa (Sj13) and shares no homology to any entries in the NCBInr database, demonstrating that Sj13 might be a schistosome-specific protein. Reverse transcriptase polymerase chain reaction, Western blotting, and immunolocalization analysis revealed Sj13 could be detected in cercaria, adult, and egg and was localized to forehead and tegument of cercaria, cell body ("cytons") of adult worm, egg shell, and epidermal plate of miracidium. Furthermore, Sj13 showed a good antigenicity when reacted with saliva or serum from schistosomiasis patients. The recombinant Sj13 (rSj13) expressed and purified from Escherichia coli was applied to detect its specific salivary antibody for schistosomiasis diagnosis by an indirect enzyme linked immunosorbent assay (ELISA). Preliminary laboratory test of 116 subjects, 40 with parasitologically proven S. japonicumm infection, 46 with other infectious diseases, and 30 negative controls exhibited 92.50% sensitivity with saliva/rSj13 and 95.00% with serum/SWAP (P > 0.05). The specificity of the ELISA using saliva/rSj13 was 92.11% versus 85.53% with serum/SWAP (P < 0.05). No direct correlations of anti-Sj13 IgG levels with egg counts in stool were observed in saliva detection. These results suggest that Sj13 specific salivary antibody detection may be useful as an antigen for the salivary diagnosis of schistosomiasis japonica and contribute to epidemiological study of schistosomiasis infection in endemic areas.
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PMID:Cloning, molecular characterization of a 13-kDa antigen from Schistosoma japonicum, Sj13, a putative salivary diagnosis candidate for Schistosomiasis japonica. 1963 40

Infection of Escherichia coli by the T7 phage leads to rapid and selective inhibition of the host RNA polymerase (RNAP)--a multi-subunit enzyme responsible for gene transcription--by a small ( approximately 7 kDa) phage-encoded protein called Gp2. Gp2 is also a potent inhibitor of E. coli RNAP in vitro. Here we describe the first atomic resolution structure of Gp2, which reveals a distinct run of surface-exposed negatively charged amino acid residues on one side of the molecule. Our comprehensive mutagenesis data reveal that two conserved arginine residues located on the opposite side of Gp2 are important for binding to and inhibition of RNAP. Based on a structural model of the Gp2-RNAP complex, we propose that inhibition of transcription by Gp2 involves prevention of RNAP-promoter DNA interactions required for stable DNA strand separation and maintenance of the "transcription bubble" near the transcription start site, an obligatory step in the formation of a transcriptionally competent promoter complex.
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PMID:T7 phage protein Gp2 inhibits the Escherichia coli RNA polymerase by antagonizing stable DNA strand separation near the transcription start site. 2013 68

The hnRNP C heterotetramer [(C1(3))C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to re-localize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis.
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PMID:Delayed kinetics of poliovirus RNA synthesis in a human cell line with reduced levels of hnRNP C proteins. 2018 23

Bluetongue virus (BTV) is a double-stranded (ds) RNA virus, classified within the genus Orbivirus, family Reoviridae, which causes bluetongue (BT), an infectious, non-contagious disease of ruminants. The virus exists as 24 distinct serotypes, which are currently identified by virus isolation and serum neutralisation assays. The most variable outer capsid protein VP2 (encoded by genome segment 2), is the primary determinant of BTV serotype. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays, based on amplification of segment 2, have been developed for identification of the five European BTV types (BTV-1, BTV-2, BTV-4, BTV-9 and BTV-16). Primer pairs were designed that are specific for each BTV serotype. The resulting RT-PCR assay was both sensitive and specific, providing BTV typing within 24 h. Perfect agreement was recorded between the RT-PCR and virus neutralisation assays. The primers for each serotype could successfully amplify the BTV isolates of that serotype from different regions and showed no cross-amplification of the most closely related BTV serotypes. RT-PCR primers were also developed for the discrimination of field and vaccine strains of BTV serotypes currently circulating in Europe. The primer pairs which could amplify field and vaccine strains of BTV-1, BTV-2, BTV-4 and BTV-9 were validated with several isolates of each serotype from various geographic origins around the world and their type specificity was again tested with the most closely related serotypes. Overall, these RT-PCR assays provide a rapid and reliable method for the identification and differentiation of field and vaccine strains of different BTV types. The primers used in this study are listed on the website of the Institute for Animal Health, Pirbright.
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PMID:Development of reverse transcriptase-polymerase chain reaction-based assays and sequencing for typing European strains of bluetongue virus and differential diagnosis of field and vaccine strains. 2042 85

Francisella tularensis, a potential bioweapon, causes a rare infectious disease called tularemia in humans and animals. The macrophage growth locus A (MglA) protein from F. tularensis associates with RNA polymerase to positively regulate the expression of multiple virulence factors that are required for its survival and replication within macrophages. The MglA protein was overproduced in Escherichia coli, purified and crystallized. The crystals diffracted to 7.5 A resolution at the Advanced Photon Source, Argonne National Laboratory and belonged to the hexagonal space group P6(1) or P6(5), with unit-cell parameters a = b = 125, c = 54 A.
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PMID:Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of macrophage growth locus A (MglA) protein from Francisella tularensis. 2044 58

Rabies, which is an acute, progressive, fatal zoonotic infectious disease, is almost always caused by the bite of rabid animals containing rabies virus in their saliva. Since there is no established specific therapy for rabies, preventive and prophylactic measures are of critical importance. In this report a case of human rabies diagnosed antemortem, was presented. A 29 year old man was admitted to Harran University Hospital (in Sanliurfa province, located at southeastern Anatolia) emergency service with symptoms of high fever, general weakness, paresthesia of the right arm, hypersalivation and dysphagia. The patient with poor socioeconomical status was living in a rural area and his anamnesis revealed a history of dog bite about five months ago. It was learned that he refused vaccination against rabies after the bite event, despite the warnings of his relatives. Shortly after admission, the patient's neurological status severly deteriorated; he became increasingly agitated. Upon the development of progressive respiratory failure, the patient underwent ventilatory support and heavily sedated with presumptive diagnosis of rabies. A nuchal skin biopsy, cerebrospinal fluid, saliva and corneal smear were sent to the Ministry of Agriculture and Rural Affairs Etlik Central Veterinary Control and Research Institute Rabies Diagnosis Laboratory in Ankara. The corneal smear was positive for rabies virus antigen revealed by direct fluorescent antibody test and saliva sample was also positive for rabies virus RNA by reverse-transcriptase polymerase chain reaction assay. Thus, on the third day of the admission the diagnosis was confirmed and on day 11, the patient was deceased due to rabies encephalitis. This case report emphasizes the importance of public education particularly in low socio-economic and socio-cultural areas, about rabies transmission and preventive and prophylactic measures that should be taken after animal bite.
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PMID:[A human rabies case with antemortem diagnosis]. 2054 67

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.
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PMID:Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection. 2073 42


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