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)

Most vaccinia virus intermediate and late mRNAs possess 3' ends that are extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A-type inclusion protein (ATI), the second largest subunit of the RNA polymerase, and the late telomeric transcripts possess homogeneous 3' ends. In the case of the ATI mRNA, it has been shown that the homogeneous 3' end is generated by a post-transcriptional endoribonucleolytic cleavage event. We have determined that the F17R gene also produces homogeneous transcripts generated by a post-transcriptional cleavage event. Mapping of in vivo mRNA shows that the major 3' end of the F17R transcript maps 1262 nt downstream of the F17R translational start site. In vitro transcripts spanning the in vivo 3' end are cleaved in an in vitro reaction using extracts from virus infected cells, and the site of cleavage is the same both in vivo and in vitro. Cleavage is not observed using extract from cells infected in the presence of hydroxyurea; therefore, the cleavage factor is either virus-coded or virus-induced during the post-replicative phase of virus replication. The cis-acting sequence responsible for cleavage is orientation specific and the factor responsible for cleavage activity has biochemical properties similar to the factor required for cleavage of ATI transcripts. Partially purified cleavage factor generates cleavage products of expected size when either the ATI or F17R substrates are used in vitro, strongly suggesting that cleavage of both transcripts is mediated by the same factor.
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PMID:Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus. 1496 83

The Saccharomyces cerevisiase protein phosphatase Fcp1 has been implicated in the regulation of transcription by RNA polymerase II, and is encoded by the essential gene FCP1. A screen was carried out for multicopy suppressors of the temperature-sensitive phenotype of two phosphatase mutants, fcp1-2 and fcp1-4. Only the wild-type FCP1 was found to suppress (complement) the fcp1-4 mutation. For fcp1-2 three second-site suppressors were identified. One contained the ORF for ZDS1. The remaining two suppressors mapped to the centromere regions of chromosomes I and V. Suppression due to centromere DNA was found to be more dependent on the CDEIII region than on other regions of the centromere. The presence of a suppressor centromere affected the level of Fcp1 protein and the overall phosphorylation state of RNA polymerase II (RNAPII) in fcp1-2 cells, but not wild-type cells, grown at both permissive and non-permissive temperatures. In addition, genetic interactions were identified between this FCP1 mutant and the genes SKP1, CEP3 and CBF1, which code for centromere binding proteins. The mechanism of suppression and regulation of Fcp1-2 protein activity by centromeric DNA is discussed.
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PMID:Genetic interactions between an RNA polymerase II phosphatase and centromeric elements in Saccharomyces cerevisiae. 1513 55

The telomeric repeat binding factor 2 (TRF2) specifically recognizes TTAGGG tandem repeats at chromosomal ends. Unexpectedly immunofluorescence studies revealed a prominent nucleolar localization of TRF2 in human cells, which appeared as discrete dots with sizes similar to those present in the nucleoplasm. The TRF2 dots did not overlap with dots stemming from the upstream binding factor (UBF) or the B23 protein. After treatment with a low concentration of actinomycin D (0.05 microg/ml), TRF2 remained in the nucleolus, although this condition selectively inhibited RNA polymerase I and led to a relocalization of UBF and B23. TRF2 was prominent in the nucleolus at G0 and S but seemed to diffuse out of the nucleolus in G2 phase. During mitosis TRF2 dispersed from the condensed chromosomes and returned to the nucleolus at cytokinesis. Treatment with low doses of actinomycin D delayed the release of TRF2 from the nucleolus as cells progressed from G2 phase into mitosis. With actinomycin D present TRF2 was detected in discrete foci adjacent to UBF in prophase, while in metaphase a complete overlap between TRF2 and UBF was observed. TRF2 was present in DNase-insensitive complexes of nucleolar extracts, whereas DNA degradation disrupted the protein-DNA complexes consisting of Ku antigen and B23. Following treatment with actinomycin D some of the mitotic cells displayed chromosome end-to-end fusions. This could be correlated to the actinomycin D-suppressed relocalization of TRF2 from the nucleolus to the telomeres during mitosis. These results support the view that the nucleolus may sequester TRF2 and thereby influences its telomeric functions.
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PMID:Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2). 1526 90

The African trypanosome, Trypanosoma brucei, is a protozoan that causes sleeping sickness in humans and N'gana in livestock. These flagellated parasites are directly exposed to immune defences as they circulate in the mammalian host bloodstream but they maintain persistent infections by undergoing antigenic variation. Central to this process is mono-allelic transcription and switching of the expressed variant-surface glycoprotein (VSG) gene which encodes the vast majority of their dense surface coat. The active telomeric VSG is transcribed by RNA polymerase I in an 'expression site body' (ESB) while transcription attenuation occurs at 'inactive' telomeres. Here, I review what is known about the molecular mechanisms involved in achieving antigenic variation and outline how we intend to exploit genome sequence and new tools, particularly RNA interference, to identify and characterise factors required for VSG regulation.
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PMID:The molecular control of antigenic variation in Trypanosoma brucei. 1535 8

Fission yeast centromeric repeats are transcribed into small interfering RNA (siRNA) precursors (pre-siRNAs), which are processed by Dicer to direct heterochromatin formation. Recently, Rpb1 and Rpb2 subunits of RNA polymerase II (RNA Pol II) were shown to mediate RNA interference (RNAi)-directed chromatin modification but did not affect pre-siRNA levels. Here we show that another Pol II subunit, Rpb7 has a specific role in pre-siRNA transcription. We define a centromeric pre-siRNA promoter from which initiation is exquisitely sensitive to the rpb7-G150D mutation. In contrast to other Pol II subunits, Rpb7 promotes pre-siRNA transcription required for RNAi-directed chromatin silencing.
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PMID:RNA Pol II subunit Rpb7 promotes centromeric transcription and RNAi-directed chromatin silencing. 1620 82

A number of methods exist to detect levels of telomerase activity and the presence of telomerase subunits in a variety of tissues. As telomerase activation seems to be an important step in tumorigenesis, accurate detection of the presence and activity of the enzyme and its subunits is vital. The original method of detecting telomerase activity was developed by Kim and coworkers in 1994, and was termed the telomeric repeat amplification protocol. This assay led to a staggering increase in the number of telomerase-associated publications in scientific journals (85 publications from 1974-1994, 5063 publications from 1994-2004). A number of methods have been described to detect telomeres and to measure their length, with the standard measurement of telomere length performed using a modification of the Southern blot protocol. RNA in situ hybridization can be performed to detect levels of the RNA component of telomerase, and standard in situ hybridization and immunohistochemistry can be applied to examine expression levels and localization of the catalytic subunit of the enzyme. Reverse transcriptase PCR has also been applied to assess expression levels of the telomerase components in various tissues. This review provides a synopsis of telomeres, telomerase, telomerase and cancer, and finally, methods for the detection of telomerase in cancer.
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PMID:Telomerase: is it the future diagnostic and prognostic tool in human cancer? 1625 32

The African trypanosome, Trypanosoma brucei, is a flagellated pathogenic protozoan that branched early from the eukaryotic lineage. Unusually, it uses RNA polymerase I (Pol I) for mono-telomeric expression of variant surface glycoprotein (VSG) genes in bloodstream-form cells. Many other subtelomeric VSG genes are reversibly repressed, but no repressive DNA sequence has been identified in any trypanosomatid. Here, we show that artificially seeded de novo telomeres repress Pol I-dependent gene expression in mammalian bloodstream and insect life-cycle stages of T. brucei. In a telomeric VSG expression site, repression spreads further along the chromosome and this effect is specific to the bloodstream stage. We also show that de novo telomere extension is telomerase dependent and that the rate of extension correlates with the expression level of the adjacent gene. Our results show constitutive telomeric repression in T. brucei and indicate that an enhanced, developmental stage-specific repression mechanism controls antigenic variation.
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PMID:Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres. 1631 18

Woc is a Drosophila zinc finger protein that shares homology with the human polypeptides ZNF261 and ZNF198 implicated in mental retardation and leukemia syndromes. We show that mutations in the woc gene cause frequent telomeric fusions in Drosophila brain cells. Woc localizes to all telomeres and most interbands of polytene chromosomes. In interbands, Woc precisely colocalizes with the initiating forms of RNA polymerase II (Pol II). To characterize the role of woc in telomere maintenance, we analyzed its relationships with Su(var)205, cav, atm, and rad50, four genes that prevent telomeric fusions; Su(var)205 and cav encode HP1 and HP1/ORC Associated Protein (HOAP), respectively. woc mutants displayed normal telomeric accumulations of both HP1 and HOAP, and mutations in cav, Su(var)205, atm, and rad50 did not affect Woc localization on polytene chromosome telomeres. Collectively, our results indicate that Woc is a transcription factor with a telomere-capping function independent of those of Su(var)205, cav, atm, and rad50.
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PMID:The putative Drosophila transcription factor woc is required to prevent telomeric fusions. 1636 9

In the fission yeast Schizosaccharomyces pombe, the RNA-Induced Transcriptional Silencing (RITS) complex has been proposed to target the chromosome via siRNA-dependent base-pairing interactions to initiate heterochromatin formation. Here we show that tethering of the RITS subunit, Tas3, to the RNA transcript of the normally active ura4+ gene silences ura4+ expression. This silencing depends on a functional RNAi pathway, requires the heterochromatin proteins, Swi6/HP1, Clr4/Suv39h, and Sir2, and is accompanied by the generation of ura4+ siRNAs, histone H3-lysine 9 methylation, and Swi6 binding. Furthermore, the ability of the newly generated ura4+ siRNAs to silence a second ura4+ allele in trans is strongly inhibited by the conserved siRNA nuclease, Eri1. Surprisingly, silencing of tethered ura4+, or ura4+ inserted within centromeric heterochromatin, or some of the endogenous centromeric repeat promoters, is not associated with changes in RNA polymerase II occupancy. These findings support a model in which targeting of nascent transcripts by RITS mediates chromatin modifications and suggest that cotranscriptional processing events play a primary role in the silencing mechanism.
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PMID:Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. 1751 98

The MLL gene is frequently involved in chromosomal translocations associated with high-risk acute leukaemia. Infant and therapy-related acute leukaemia patients display chromosomal breakpoints preferentially clustered in the telomeric portion of the MLL breakpoint cluster region (SCII). Here, we demonstrate that SCII colocalizes with a gene-internal promoter element in the mouse and human MLL gene, respectively. The mRNA generated encodes an N-terminally truncated version of MLL that still exhibits many functional regions, including the C-terminal SET-domain. Etoposide-induced DNA double-strand breaks colocalize with the binding site of RNA polymerase II and the transcription initiation region, but not with a nearby Topo II consensus sequence. Thus, the observed genomic instability of the human MLL gene is presumably linked to transcriptional processes. The consequences of this novel finding for the creation of chromosomal translocations, the biology of the MLL protein and for MLL-mediated acute leukaemia are discussed.
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PMID:Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene. 1698 45


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