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

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a prospective clinical and virological study of 18 patients undergoing orthotopic liver transplantation, selected because of hepatitis C virus (HCV) RNA positivity before transplantation. Nine of the 18 patients (50%) developed chronic active hepatitis (CAH) in liver allografts during the first year posttransplantation; hepatitis was first observed between 6 and 25 weeks posttransplantation. HCV viremia was measured for all patients before transplantation and on posttransplantation days 3, 7, and 14, and months 1, 6, 12, and 24 to 41, by quantitative competitive RNA polymerase chain reaction (QC-PCR). HCV RNA levels on posttransplantation days 3, 7, and 14 were significantly higher among patients who subsequently developed CAH versus those who did not (P < .02 by t-test and Mann-Whitney test on all three dates). However, HCV RNA levels in sera obtained at 1, 6, and 12 months posttransplantation did not correlate with CAH at 1 year or with HCV genotype determined in posttransplantation sera. At least two serial liver biopsy specimens from each patient were stained for HCV nonstructural 4 (NS4) antigen by immunohistochemistry. The intensity of cytoplasmic staining of NS4 antigen was significantly higher for specimens with CAH versus those without CAH (P = .028 by chi 2). Three patients developed bridging fibrosis in liver allografts during the first year after transplantation; all three patients had intense (3+) immunostaining for NS4 antigen, and the infecting genotypes were 1a, 1b, and 1a plus 1b, respectively. In summary, the 18 patients all developed high-titer viremia by 1 month after liver transplantation, whereas CAH developed in 50% of allografts during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Persistent hepatitis C virus infection after liver transplantation: clinical and virological features. 754 38

Twelve patients with Galerina Autumnalis (GA) poisoning were treated. Amatoxin and phallotoxin are the principal toxins of GA. After absorption from intestine into the liver, the toxins combine with RNA polymerase, resulting in block of messenger (mRNA) synthesis, hepatocellular damage, hepatitis, hepatic necrosis, serious coagulation abnormalities and DIC. The clinical characteristics are long latent period, short period of "pseudo-remission" and serious liver dysfunction. These were pathologically confirmed by autopsy. Our experiences with this poisoning are as follows: treatment should be carried out as early as possible, especially with gastric lavage and catharsis and special attention paid to the "pseudo-remission".
...
PMID:[A clinical analysis of twelve patients with Galerina autumnalis poisoning]. 803 56

We have used a full-length cDNA clone of a mouse hepatitis virus strain A59 defective interfering (DI) RNA, pMIDI-C, and cassette mutagenesis to study the mechanism of coronavirus subgenomic mRNA synthesis. Promoter sequences closely resembling those of subgenomic mRNAs 3 and 7 were inserted into MIDI-C. Both subgenomic RNA promoters gave rise to the synthesis of a subgenomic DI RNA in virus-infected and DI RNA-transfected cells. From a mutagenic analysis of the promoters we concluded the following. (i) The extent of base pairing between the leader RNA and the intergenic promoter sequence does not control subgenomic RNA abundance. (ii) Promoter recognition does not rely on base pairing only. Presumably, transcription initiation requires recognition of the promoter sequence by the transcriptase. (iii) Fusion of leader and body sequences takes place at multiple--possibly random--sites within the intergenic promoter sequence. A model is presented in which, prior to elongation, the leader RNA is trimmed by a processive 3'-->5' nuclease.
...
PMID:Subgenomic RNA synthesis directed by a synthetic defective interfering RNA of mouse hepatitis virus: a study of coronavirus transcription initiation. 818 3

The expression of carcinoembryonic antigen (CEA)-related glycoproteins that have been associated with intercellular adhesion and that serve as receptors for mouse hepatitis virus (MHV) was analyzed in cells from the immune system of BALB/c mice using immunolabeling and RNA polymerase chain reaction amplification of receptor transcripts. These glycoproteins, which are called biliary glycoproteins, were highly expressed in B lymphocytes, including cells of the B-1a (CD5+) lineage, and in macrophages, but were not detectable in resting T lymphocytes. Similarly, murine cell lines of B cell and macrophage origin expressed messenger RNA encoding CEA-related molecules, while the corresponding mRNA was only slightly detectable in a T cell line. These CEA-related cell adhesion glycoproteins were also expressed in endothelial cells. Therefore, their specific interaction with their so far unknown ligand may be of functional importance in cellular interactions in the immune response. Monoclonal antibody directed against these glycoproteins blocked MHV-A59 infection of the B cell-derived SP20 cell line. Thus, the functional receptors for MHV on B lymphocytes, like those on murine fibroblasts, are isoforms of CEA-related glycoproteins. Treatment of B cells with anti-receptor antibody also blocked B cell-mediated cytotoxicity against MHV-A59-infected fibroblasts, indicating that this phenomenon is mediated by interaction of viral attachment protein on the infected target cells with specific CEA-related receptor glycoproteins on the effector B cells.
...
PMID:B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. 820 98

The recently characterized fecal-orally transmitted agent of hepatitis E (formerly known as enterically transmitted non-A, non-B hepatitis) has been determined to be a new type of positive strand RNA virus. The complete sequencing of four different geographic isolates of the hepatitis E virus (HEV) has confirmed a similar genetic organization not previously recognized in nonenveloped positive strand RNA viruses. The approximately 7.5 kb RNA genome (including polyA tail) has nonstructural genes located at the 5' end and structural genes at the 3' end. Expression of these viral genes occurs in at least 3 different forward open reading frames. The largest open reading frame begins 27 nucleotides (nt) downstream of the apparent noncoding 5' end and extends 5,079 nt. Multiple nonstructural gene motifs/domains have been recognized in this 5' ORF1 including a methyltransferase, a papain-like protease, a helicase and the RNA-dependent, RNA polymerase. The second major ORF2 begins 37nt downstream of ORF1 and extends 1980 nt before terminating 65 nt upstream of the polyadenylation site. A third ORF of only 369 nt was identified by immunoscreening experiments as encoding an immunogenic epitope of the virus. Expression of the downstream ORF2 may occur through internal subgenomic RNA initiation at a sequence element found to have homology to internal RNA initiation sequences in Sindbis virus. This element in the HEV genome maps near the apparent 5' end of one of two identified subgenomic messages. The genomic organization and expression of HEV will be discussed and a hypothesis presented regarding the viral replication strategy.
...
PMID:Molecular organization and replication of hepatitis E virus (HEV). 821 99

Human hepatitis delta virus has a single-stranded circular RNA genome that replicates by RNA-directed RNA synthesis. The virus encodes only a single protein, the delta antigen, which both is small (22 kDa) and lacks sequence homology to known RNA polymerases, suggesting that the virus employs a cellular polymerase for replication. Consistent with this suggestion, we have used homogenized nuclei from a human hepatoma cell line, HepG2, to demonstrate RNA-directed RNA synthesis from both genomic hepatitis delta virus RNA and its complement, the antigenomic RNA. RNA polymerase II was responsible for this transcription because the reaction was inhibited both by low doses of alpha-amanitin and by a monoclonal antibody specific for polymerase II. In addition, it was found that the majority of the RNA products were processed, presumably by self-cleavage and self-ligation, to produce covalently closed circular molecules.
...
PMID:The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates. 823 Apr 19

The nucleotide sequence of the human coronavirus 229E (HCV 229E) RNA polymerase gene and the 5' region of the genome has been determined. The polymerase gene is comprised of two large open reading frames, ORF1a and ORF1b, that contain 4086 and 2687 codons, respectively. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. The in vitro translation of SP6 transcripts which include HCV 229E sequences encompassing the ORF1a/ORF1b junction show that expression of ORF1b can be mediated by ribosomal frame-shifting. The predicted translation products of ORF1a (454,200 molecular weight) and ORF1a/1b (754,200 molecular weight) have been compared to the predicted RNA polymerase gene products of infectious bronchitis virus (IBV) and murine hepatitis virus (MHV) and conserved structural features and putative functional domains have been identified. This analysis completes the nucleotide sequence of the HCV 229E genome.
...
PMID:Nucleotide sequence of the human coronavirus 229E RNA polymerase locus. 833 38

Transcription and replication of hepatitis delta virus (HDV) RNA is thought to be performed by host RNA polymerase II. The mechanism which enables polymerase II to use RNA as a template is unclear. However, since extensive intramolecular complementarity allows HDV RNA to form a rod-shaped structure, it is possible that the mostly double-stranded HDV RNA may resemble double-stranded DNA in structure, and can thus be used by RNA polymerase II as a template. To investigate this possibility, we examined whether the cDNA counterpart of HDV RNA contains a promoter and thus can drive the transcription and replication of HDV RNA. Circularized monomers of HDV cDNA, when transfected into various cell lines, were found to generate both monomeric and dimeric forms of HDV RNA and hepatitis delta antigen at levels comparable to those generated with HDV cDNA multimers under the control of a SV40 late promoter, suggesting that HDV cDNA contains endogenous promoters. Using chloramphenicol acetyltransferase and human growth hormone as reporter genes, the specific promoter activity for the synthesis of antigenomic HDV RNA was localized to a 29-nucleotide region (nucleotides 1650-1679), although an additional 224-nucleotide upstream region was also necessary for maximum activity. Similarly, promoter activity for the synthesis of genomic RNA was localized to a 160-nucleotide region around position 1679 that overlapped with the antigenomic promoter region. Since these regions are in a highly conserved double-stranded region of HDV RNA, they may represent RNA promoters recognized by RNA polymerase II. This result also suggests a convenient method, using circularized monomer HDV cDNA, to study HDV RNA replication.
...
PMID:Endogenous promoters can direct the transcription of hepatitis delta virus RNA from a recircularized cDNA template. 837 36

All of the defective interfering (DI) RNAs of mouse hepatitis virus (MHV) contain both the 5' and 3' ends of the viral genomic RNA, which presumably include the cis sequences required for RNA replication. To define the replication signal of MHV RNA, we have used a vaccinia virus-T7 polymerase-transcribed MHV DI RNA to study the effects of sequence deletion on DI RNA replication. Following infection of susceptible cells with a recombinant vaccinia virus expressing T7 RNA polymerase, various cDNA clones derived from a DI RNA (DIssF) of the JHM strain of MHV, which is a 3.5-kb naturally occurring DI RNA, behind a T7 promoter were transfected. On superinfection with a helper MHV, the ability of various DI RNAs to replicate was determined. Serial deletions from the middle of the RNA toward both the 5' and 3' ends demonstrated that 859 nucleotides from the 5' end and 436 nucleotides from the 3' end of the MHV RNA genome were necessary for RNA replication. Surprisingly, an additional stretch of 135 nucleotides located at 3.1 to 3.3 kb from the 5' end of the genome was also required. This stretch is discontiguous from the 5'-end cis replication signal and is present in all of the naturally occurring DI RNAs studied so far. The requirement for a long stretch of 5'- and 3'-end sequences predicts that the subgenomic MHV mRNAs cannot replicate. The efficiency of RNA replication varied with different cDNA constructs, suggesting possible interaction between different regions of DI RNA. The identification of MHV RNA replication signals allowed the construction of an MHV DI-based expression vector, which can express foreign genes, such as the chloramphenicol acetyltransferase gene.
...
PMID:Deletion mapping of a mouse hepatitis virus defective interfering RNA reveals the requirement of an internal and discontiguous sequence for replication. 839 72

Transcription and replication of hepatitis delta virus (HDV) RNA are performed by the cellular enzyme RNA polymerase II (Pol II). As DNA is the normal template for Pol II, the enzyme must undergo template switching. The mechanism for this is unknown, but since HDV RNA can form a rod-like molecule by extensive intramolecular base pairing, it has been suggested that a double-stranded region(s) of HDV RNA serves as a recognition site for Pol II. A bidirectional promoter has been identified previously on HDV cDNA (T. B. Macnaughton, M. R. Beard, M. Chao, E. J. Gowans, and M. M. C. Lai, Virology 196:629-636, 1993). In the present study, genomic RNA corresponding to this region was able to direct the synthesis of antigenomic RNA in a nuclear extract transcription reaction, whereas genomic RNA species containing a mutation that resulted in a replication-defective phenotype were unable to do so. Thus, this region, the location of which is defined as nucleotides 1608 to 1669 on the basis of a highly conserved structure, represents a RNA-RNA promoter. Computer analysis of the RNA secondary structure predicted that the promoter contains two bulge regions in a stem-loop structure which encompasses a GC-rich motif. This predicted model was confirmed by enzyme digestion and primer extension analysis. The promoter is located at one end of the rod and has some homology with the simian virus 40 late promoter. A number of other mutations were introduced within this region, and expression plasmids were constructed to examine the effects of mutations in the promoter on HDV replication. Disruption of the overall secondary structure, particularly the bulge regions, totally inhibited HDV RNA replication.
...
PMID:Identification and characterization of a hepatitis delta virus RNA transcriptional promoter. 876 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---