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)

The organization of the U3, U8, and U13 small nucleolar ribonucleoproteins (snoRNPs) has been investigated in HeLa cells using antisense DNA and 2'-OMe RNA oligonucleotides. Oligomers corresponding to deoxynucleotides that target RNase H degradation of intact RNP particles were synthesized and used for fluorescence in situ hybridization. U3 and U13 are distributed throughout the nucleolus and colocalize with anti-fibrillarin antibodies. U8, however, is organized in discrete ring-like structures near the center of the nucleolus and surround bright punctate regions visualized with anti-RNA polymerase I and anti-UBF/NOR-90 antibodies. In decondensed nucleoli, a necklace of smaller ring-like structures of U8 RNA appear. A model for the recruitment of U8 (and presumably other processing factors) to the sites of rRNA transcription is discussed. Hybridization to mitotic cells showed that unlike pol I and NOR-90, U8 is dispersed into the cytoplasm during mitosis. The subnucleolar organization of U8 is consistent with its demonstrated participation in early intermediate steps in pre-rRNA processing. In contrast, the more dispersed intranucleolar distribution of U3 agrees with its putative involvement in both early and late steps of rRNA maturation. These studies illustrate the feasibility of mapping functional domains within the nucleolus by correlating the in vitro activities of small nuclear RNPs with their in situ locations.
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PMID:Organization of small nucleolar ribonucleoproteins (snoRNPs) by fluorescence in situ hybridization and immunocytochemistry. 753 31

We are investigating the roles of RNA synthesis, chromatin structure and nuclear matrix organization in establishing and maintaining transcription domains, using mitogen stimulated lymphocytes as a model system. In a continuing study, the effects of the RNA polymerase inhibitor DRB and of its removal on nuclear organization have been examined by EM cytochemistry and by immunofluorescence labelling of the nuclear matrix PI1, Sm and nucleolar fibrillarin antigens. Chromatin, interchromatin granules and nucleoli were extensively restructured after DRB, as were matrix antigens. According to cytochemical staining properties, the conformation of DRB-induced condensed chromatin resembled that in partially stimulated lymphocytes. The nucleoplasmic fibrogranular RNP network appeared little altered, but the fibrillar proteinaceous interchromatinic regions, interpreted as representing the nuclear matrix in situ, were more affected. After removal of DRB, nuclei recovered the organization and transcriptional activity of controls within 8 h. These results suggest that the matrix subtending transcription domains remains stable when transcription is arrested, even though the chromatin and individual RNP components of the domains are disorganized. The data further indicate that absence of transcription is not solely accountable for the highly aggregated state of the chromatin in resting lymphocytes.
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PMID:Reversible disassembly of transcription domains in lymphocyte nuclei during inhibition of RNA synthesis by DRB. 769 22

When cells enter mitosis, RNA synthesis ceases. Yet the RNA polymerase I (pol I) transcription machinery involved in the production of pre-rRNA remains bound to the nucleolus organizing region (NOR), the chromosome site harboring the tandemly repeated rRNA genes. Here we examine whether rDNA transcription units are transiently blocked or "frozen" during mitosis. By using fluorescent in situ hybridization we were unable to detect nascent pre-rRNA chains on the NORs of mouse 3T3 and rat kangaroo PtK2 cells. Appropriate controls showed that our approach was sensitive enough to visualize, at the light microscopic level, individual transcriptionally active rRNA genes both in situ after experimental unfolding of nucleoli and in chromatin spreads ("Miller spreads"). Analysis of the cell cycle-dependent redistribution of transcript-associated components also revealed that most transcripts are released from the rDNA at mitosis. Upon disintegration of the nucleolus during mitosis, U3 small nucleolar RNA (snoRNA) and the nucleolar proteins fibrillarin and nucleolin became dispersed throughout the cytoplasm and were excluded from the NORs. Together, our data rule out the presence of "frozen Christmas-trees" at the mitotic NORs but are compatible with the view that inactive pol I remains on the rDNA. We propose that expression of the rRNA genes is regulated during mitosis at the level of transcription elongation, similarly to what is known for a number of genes transcribed by pol II. Such a mechanism may explain the decondensed state of the NOR chromatin and the immediate transcriptional reactivation of the rRNA genes following mitosis.
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PMID:A possible mechanism for the inhibition of ribosomal RNA gene transcription during mitosis. 773 Mar 96

Visualization of nuclear architecture is key to the understanding of the association between RNA synthesis and processing. This architecture is obscured by the high density of components in most nuclei. We have developed a method of spreading nuclei and nucleoli that reduces overlap of weakly associated components. Strong interactions among nuclear components are not disrupted by this method. Spread nucleoli remained structurally distinct and functionally competent in ribosomal RNA synthesis. Nascent ribosomal RNA colocalized with RNA polymerase I and fibrillarin, a protein required for processing of ribosomal RNA. Colocalization of nascent transcripts and fibrillarin was seen in nucleoli spread over several microns, suggesting a strong interaction. These data suggest that nucleoli are superassemblies of bipartite domains, each composed of a ribosomal RNA synthesis center tightly associated with areas likely to be involved in ribosomal RNA processing.
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PMID:Nuclear spreads: I. Visualization of bipartite ribosomal RNA domains. 782 12

Patients with hepatocellular carcinoma (HCC) develop autoantibodies to nuclear and nucleolar antigens (ANAs) which can be readily detected by immunofluorescence on cell substrates. The frequency of ANAs in HCC is 31% (57/184). The identity of three autoantigens was established as: NOR-90, nucleolus organizer region (doublet) polypeptides involved in RNA polymerase I transcription; fibrillarin, a component of nucleolar U3 RNP involved in pre-ribosomal RNA processing, and nucleophosmin/protein B23, a nucleolar protein involved in ribosome maturation and cell proliferation. Changes in ANAs were observed in some patients during transition from chronic liver disease to HCC and were manifested as seroconversion from ANA-negative to ANA-positive status by an increase in titers and changes in ANA specificities. Serum from a patient during this transition period was used to isolate a cDNA clone encoding a novel nuclear protein with structural motifs characteristic of a family of splicing factors. These observations support the notion that ANA responses in HCC might be driven by intracellular events related to transformation from the stage of chronic injury to the stage of malignancy. Changes in ANA profiles which were observed to precede clinically diagnosed HCC in some patients might be early markers of transformation.
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PMID:Autoantibodies in viral hepatitis-related hepatocellular carcinoma. 840 52

We have previously constructed mutants of Saccharomyces cerevisiae in which the gene for the second-largest subunit of RNA polymerase I (Pol I) is deleted. In these mutants, rRNA is synthesized by RNA polymerase II from a hybrid gene consisting of the 35S rRNA coding region fused to the GAL7 promoter on a plasmid. These strains thus grow in galactose but not glucose media. By immunofluorescence microscopy using antibodies against the known nucleolar proteins SSB1 and fibrillarin, we found that the intact crescent-shaped nucleolar structure is absent in these mutants; instead, several granules (called mininucleolar bodies [MNBs]) that stained with these antibodies were seen in the nucleus. Conversion of the intact nucleolar structure to MNBs was also observed in Pol I temperature-sensitive mutants at nonpermissive temperatures. These MNBs may structurally resemble prenucleolar bodies observed in higher eukaryotic cells and may represent a constituent of the normal nucleolus. Furthermore, cells under certain conditions that inhibit rRNA synthesis did not cause conversion of the nucleolus to MNBs. Thus, the role of Pol I in the maintenance of the intact nucleolar structure might include a role as a structural element in addition to (or instead of) a functional role to produce rRNA transcripts. Our study also shows that the intact nucleolar structure is not absolutely required for rRNA processing, ribosome assembly, or cell growth and that MNBs are possibly functional in rRNA processing in the Pol I deletion mutants.
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PMID:Structural alterations of the nucleolus in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. 845 21

A growing list of small nucleolar RNAs (snoRNAs) has been characterized in eukaryotes. They are transcribed by RNA polymerase II or III; some snoRNAs are encoded in the introns of other genes. The nonintronic polymerase II transcribed snoRNAs receive a trimethylguanosine cap, probably in the nucleus, and move to the nucleolus. snoRNAs are complexed with proteins, sometimes including fibrillarin. Localization and maintenance in the nucleolus of some snoRNAs requires the presence of initial precursor rRNA (pre-rRNA). Many snoRNAs have conserved sequence boxes C and D and a 3' terminal stem; the role of these features are discussed. Functional assays done for a few snoRNAs indicate their roles in rRNA processing for cleavage of the external and internal transcribed spacers (ETS and ITS). U3 is the most abundant snoRNA and is needed for cleavage of ETS1 and ITS1; experimental results on U3 binding sites in pre-rRNA are reviewed. 18S rRNA production also needs U14, U22, and snR30 snoRNAs, whereas U8 snoRNA is needed for 5.8S and 28S rRNA production. Other snoRNAs that are complementary to 18S or 28S rRNA might act as chaperones to mediate RNA folding. Whether snoRNAs join together in a large rRNA processing complex (the "processome") is not yet clear. It has been hypothesized that such complexes could anchor the ends of loops in pre-rRNA containing 18S or 28S rRNA, thereby replacing base-paired stems found in pre-rRNA of prokaryotes.
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PMID:Small nucleolar RNA. 872

We have employed immunocytochemical procedures to localise the nucleolar protein fibrillarin and the enzyme RNA polymerase I in the numerous dense fibrillar bodies (nucleolar precursor bodies) which appear in the nuclei of mammalian early embryos. The aim of this study was to search for relationships between the localisation of these proteins, the changes in the structure of the nucleolar precursor bodies and the resumption of rRNA gene transcription during mouse early embryogenesis. Three human autoimmune sera which recognised fibrillarin and a rabbit antiserum created against RNA polymerase I were employed for fluorescence and electron microscopic immunocytochemical assays. A statistical analysis was also applied. Immunocytochemistry revealed that fibrillarin and RNA polymerase I showed the same localisation in the nucleolar precursor bodies. These proteins were immunolocalised only from the late 2-cell stage onward. Fibrillarin was initially detected at the periphery of the nucleolar precursor bodies and the labelling gradually increased until the morula and blastocyst stages, where normally active nucleoli are found. The pattern of increase of fibrillarin during early embryogenesis shows a parallelism with the rise in rRNA gene transcription occurring during these embryonic stages, and a possible correlation between these two phenomena is suggested. Results demonstrated that nucleolar precursor bodies differ in their biochemical composition from the nucleolus and also from the prenucleolar bodies which appear during mitosis. When anti-fibrillarin antibodies were microinjected into the male pronucleus of mouse embryos to analyse the functions of fibrillarin during early development, they partially blocked the early development of mouse embryos and only 23.8% of injected embryos reach the blastocyst stage.
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PMID:Immunocytochemical localisation of the nucleolar protein fibrillarin and RNA polymerase I during mouse early embryogenesis. 873 70

The Ki-67 antigen is detected in proliferating cells in all phases of the cell division cycle. Throughout most of interphase, the Ki-67 antigen is localised within the nucleous. To learn more about the relationship between the Ki-67 antigen and the nucleolus, we have compared the distribution of Ki-67 antibodies with that of a panel of antibodies reacting with nucleolar components by confocal laser scanning microscopy of normal human dermal fibroblasts in interphase stained in a double indirect immunofluorescence assay. During early G1, the Ki-67 antigen is detected at a large number of discrete foci throughout the nucleoplasm, extending to the nuclear envelope. During S-phase and G2, the antigen is located in the nucleolus. Double indirect immunofluorescence studies have revealed that during early to mid G1 the Ki-67 antigen is associated with reforming nucleoli within discrete domains which are distinct from domains containing two of the major nucleolar antigens fibrillarin and RNA polymerase I. Within mature nucleoli the Ki-67 antigen is absent from regions containing RNA polymerase I and displays only partial co-localisation within domains containing either fibrillarin or B23/nucleophosmin. Following disruption of nucleolar structure, induced by treatment of cells with the drug 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole or with actinomycin D, the Ki-67 antigen translocates to nucleoplasmic foci which are associated with neither fibrillarin nor RNA polymerase I. However, in treated cells the Ki-67 Ag remains associated with, but not co-localised to, regions containing B23/nucleophosmin. Our observations suggest that the Ki-67 antigen associates with a fibrillarin-deficient region of the dense fibrillar component of the nucleolus. Integrity of this region is lost following either nucleolar dispersal or nucleolar segregation.
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PMID:Localisation of the Ki-67 antigen within the nucleolus. Evidence for a fibrillarin-deficient region of the dense fibrillar component. 879 15

TLS (FUS) and the related gene EWS encode the N-terminal portion of many fusion oncoproteins involved in human sarcomas and leukemia. TLS is an RNA-binding nuclear protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. When RNA polymerase II is inhibited, TLS immunostaining in the nucleus is dramatically altered, from its normal diffuse nucleoplasmic pattern to accumulation in dense nuclease-resistant aggregates. Co-immunostaining with antibodies to fibrillarin or p80 coilin and immunoelectron microscopy revealed that the TLS aggregates are associated with the nucleolus and are distinct from other known structures such as the coiled body or the interchromatin granule. Injection of cells with an oligodeoxynucleotide that disrupts splicing does not result in redistribution of TLS, indicating that the event is specific to inhibition of transcription. Oncoproteins that contain the N-terminal domain from either TLS, EWS or their Drosophila homologue, SARFH (CAZ), are also targeted to the same structure. These findings suggest a correlation between the topogenic and transforming activities of TLS and EWS N-termini and imply the existence of cellular targets that are shared by the germ-line encoded proteins and their oncogenic derivatives.
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PMID:A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited. 905 42


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