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)

Nuclear antigen 1 (EBNA-1) is one of the key functions of the oncogenic DNA virus, Epstein-Barr virus (EBV), and is the only viral protein consistently expressed in EBV-associated malignancies. EBNA-1 binds in a site-specific manner to the viral DNA and is essential for viral replication, as well as for maintaining the genome as an extrachromosomal episome within infected cells. EBNA-1 is not recognized by the cellular immune system. Here we demonstrate that, in addition to its known DNA binding properties, EBNA-1 can also act as a strong RNA binding protein, interacting with diverse substrates in vitro, including the EBV-encoded RNA polymerase III transcript EBER1 and the HIV-encoded transactivation response (TAR) element. We also show that EBNA-1 can bind exon sequences derived from its own RNA expressed from the Fp promoter, as found in Burkitt's lymphoma-related cells and in nasopharyngeal carcinomas. EBNA-1 has been identified as a component in an RNA complex; moreover, an anti-EBNA-1 antibody 1H4-1, that does not inhibit DNA binding, blocks binding to RNA. Arginine/glycine-containing (so-called 'RGG') motifs have been found in an increasing number of proteins that interact with RNA. The EBV antigen contains three potential 'RGG' motifs located around an internal glycine/alanine-rich repetitive sequence in the protein, and outside the region of EBNA-1 mapped previously as essential for viral DNA replication and other functionally defined properties. These motifs could be involved in the observed binding between EBNA-1 and RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:EBNA-1, the major nuclear antigen of Epstein-Barr virus, resembles 'RGG' RNA binding proteins. 795 53

The Nun protein of phage HK022 is an RNA binding protein of the arginine-rich motif family. Nun binds the phage lambda boxB RNA sequence (BOXB) on nascent lambda transcripts and arrests transcription elongation. Binding to BOXB is inhibited by Zn2+ and stimulated by the Escherichia coli NusA protein. Deletion of the Nun C-terminal region enhances BOXB binding and makes it independent of Zn2+ and NusA. The C terminus of Nun thus appears to interfere with the N-terminal RNA binding motif. NusA relieves this interference by binding to the Nun C terminus and forming a complex with Nun and BOXB. However, NusA also inhibits transcription arrest in vitro, in the absence of the other Nus factors. Nun deleted for its C terminus fails to bind RNA polymerase (RNAP) (RNAP) or NusA in vitro or to arrest transcription in vivo or in vitro. Our findings are consistent with the idea that NusA inhibits transcription arrest by binding to the Nun C terminus, thus blocking the interaction between Nun and RNAP. NusG, NusB, and NusE factors restore transcription arrest, presumably by promoting transfer of Nun from NusA to RNAP.
...
PMID:Escherichia coli NusA is required for efficient RNA binding by phage HK022 nun protein. 946 52

As a result of the t(11;22)(q24;q12) chromosomal translocation characterizing the Ewing family of tumors (ET), the amino terminal portion of EWS, an RNA binding protein of unknown function, is fused to the DNA-binding domain of the ets transcription factor Fli1. The hybrid EWS-Fli1 protein acts as a strong transcriptional activator and, in contrast to wildtype Fli1, is a potent transforming agent. Similar rearrangements involving EWS or the highly homologous TLS with various transcription factors have been found in several types of human tumors. Employing yeast two-hybrid cloning we isolated the seventh largest subunit of human RNA polymerase II (hsRPB7) as a protein that specifically interacts with the amino terminus of EWS. This association was confirmed by in vitro immunocoprecipitation. In nuclear extracts, hsRPB7 was found to copurify with EWS-Fli1 but not with Fli1. Overexpression of recombinant hsRPB7 specifically increased gene activation by EWS-chimeric transcription factors. Replacement of the EWS portion by hsRPB7 in the oncogenic fusion protein restored the transactivating potential of the chimera. Our results suggest that the interaction of the amino terminus of EWS with hsRPB7 contributes to the transactivation function of EWS-Fli1 and, since hsRPB7 has characteristics of a regulatory subunit of RNA polymerase II, may influence promoter selectivity.
...
PMID:Oncogenic EWS-Fli1 interacts with hsRPB7, a subunit of human RNA polymerase II. 970 26

Transcription regulation of genes active in the cardiovascular system is a complex process, involving DNA and RNA binding proteins. Nucleic acid binding proteins bind to the regulatory DNA and interact with other proteins, including RNA polymerase to initiate and control the level of transcription. The RNA binding proteins have a function in spliceosome formation and in stabilising mRNA. In this review the currently available molecular approaches to analyse regulatory DNA in relation to DNA binding proteins are discussed. Similar techniques that have been developed for RNA binding protein studies are included. In addition to an explanation of the various methods, examples are provided from DNA-protein interactions on genes active in the cardiovascular system, together with strategies for identification and characterisation of new nucleic acid binding proteins active in cardiac or vascular cell types.
...
PMID:Hunting down nucleic acid binding factors in the cardiovascular system. 970 91

The BglG protein is a transcriptional antiterminator acting within the beta-glucoside operon of Escherichia coli by binding to a specific sequence motif in the growing mRNA. Binding of BglG prevents formation of the terminator stem-loop structure, thereby causing the RNA polymerase to continue transcription. Activity of BglG is modulated in a complex way by antagonistically acting phosphorylations in response to the availability of beta-glucosidic substrates and to the catabolic state of the cell. The enzymes responsible for these phosphorylations are members of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) that represents a central carbohydrate uptake and signal transduction system. As these enzymes are believed to all form higher-order complexes associated with the cytoplasmic membrane, we tested whether or not BglG would remain active when artificially anchored to its presumptive site of regulation, the inner membrane. We show that the membrane-anchored protein indeed efficiently catalyzes transcriptional antitermination. Moreover, the membrane-attached BglG remains regulated by the PTS. Thus, a membrane-bound regulatory RNA binding protein can potentially interact fast enough with its target within the nascent transcript and cause the transcriptional machinery to proceed, before transcriptional termination would occur. Consequently, there is no principal necessity for an RNA-binding transcriptional regulator like BglG to leave the inner membrane, a potential regulatory site, and migrate to the site of transcription, the nucleoid.
...
PMID:Efficient transcriptional antitermination from the Escherichia coli cytoplasmic membrane. 1132 58

H/ACA small nucleolar ribonucleoprotein particles (snoRNPs) are essential for the maturation and pseudouridylation of the precursor of rRNAs and other stable RNAs. Although the RNA and protein components of these RNPs have been identified, the mechanisms by which they are assembled in vivo are poorly understood. Here we show that the RNA binding protein Naf1p, which is required for H/ACA snoRNPs stability, associates with RNA polymerase II-associated proteins Spt16p, Tfg1p, and Sub1p and with H/ACA snoRNP proteins. Chromatin immunoprecipitation experiments show that Naf1p and the pseudouridylsynthetase Cbf5p cross-link specifically with the chromatin of H/ACA small nucleolar RNA (snoRNA) genes. Naf1p and Cbf5p cross-link predominantly with the 3' end of these genes, in a pattern similar to that observed for transcription elongation factor Spt16p. Cross-linking of Naf1p to H/ACA snoRNA genes requires active transcription and intact H/ACA snoRNA sequences but does not require the RNA polymerase II CTD kinase Ctk1p. These results suggest that Naf1p and Cbf5p are recruited in a cotranscriptional manner during H/ACA snoRNP assembly, possibly by binding to the nascent H/ACA snoRNA transcript during elongation or termination of transcription of H/ACA snoRNA genes.
...
PMID:Cotranscriptional recruitment of the pseudouridylsynthetase Cbf5p and of the RNA binding protein Naf1p during H/ACA snoRNP assembly. 1579 13

The exosome complex is involved in multiple RNA processing and degradation pathways. How exosome is recruited to particular RNA substrates and then chooses between RNA processing and degradation modes remains unclear. We find that the RNA binding protein Nrd1, complexed with its partners Nab3, Sen1, and cap binding complex, physically interacts with the nuclear form of exosome. Nrd1 stimulates the RNA degradation activity of the exosome in vitro. However, Nrd1 can also block 3' to 5' degradation by the exosome at some Nrd1 binding sites. Nrd1 mutations share some phenotypes with exosome mutants, including increased readthrough transcription from several mRNA and sn/snoRNA genes. Therefore, Nrd1 may recruit exosome to RNA and influence the choice between processing and degradation. Since Nrd1 is known to bind RNA polymerase II and be important for sn/snoRNA 3' end processing, Nrd1 may link transcription and RNA 3' end formation with surveillance by the exosome.
...
PMID:Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II transcripts. 1642 13

The perinucleolar compartment (PNC) is a dynamic, irregularly shaped, and electron-dense nuclear structure that is physically associated with the nucleolus (1). It is found predominantly in transformed cells and various cancer tissues, and rarely in normal cells (1). The components of the PNC described to date include several small RNAs transcribed by RNA polymerase (pol) III, and several RNA binding proteins of which some are primarily implicated in pre-messenger RNA (mRNA) processing (2). The current working model suggests that the PNC is a dynamic functional organelle involved in the metabolism and trafficking of a subset of newly synthesized pol III RNAs in transformed cells. The PNC can be localized and visualized in tissue sections by a immunohistochemical technique using the mouse monoclonal antibody SH54 (3), which specifically recognizes the RNA binding protein PTB (polypyrimidine tract binding protein), which is highly concentrated in the PNC and is used as a marker for PNC detection.The prevalence of PNCs has been found to be correlated with disease progression in breast cancer (3) and in tumors from other tissues, including prostate, colon, ovary, and endometrium (our unpublished studies). PNC prevalence increases with the degree of malignancy and reaches nearly 100% in distant metastases. A high PNC prevalence is associated with poor prognosis (our unpublished studies) (3). In this chapter, we describe methods, which are still under development, for PNC detection and PNC prevalence scoring. Due to the intrinsic limitations of immunocytochemistry using peroxidase assays, the signal intensity can vary from experiment to experiment. Studies are underway to optimize an automated protocol to increase its reproducibility and accuracy.
...
PMID:The perinucleolar compartment (PNC): detection by immunohistochemistry. 1895 Nov 67

Hepatitis delta virus (HDV) encodes one protein, hepatitis delta antigen (deltaAg), a 195-amino-acid RNA binding protein essential for the accumulation of HDV RNA-directed RNA transcripts. It has been accepted that deltaAg localizes predominantly to the nucleolus in the absence of HDV genome replication while in the presence of replication, deltaAg facilitates HDV RNA transport to the nucleoplasm and helps redirect host RNA polymerase II (Pol II) to achieve transcription and accumulation of processed HDV RNA species. This study used immunostaining and confocal microscopy to evaluate factors controlling the localization of deltaAg in the presence and absence of replicating and nonreplicating HDV RNAs. When deltaAg was expressed in the absence of full-length HDV RNAs, it colocalized with nucleolin, a predominant nucleolar protein. With time, or more quickly after induced cell stress, there was a redistribution of both deltaAg and nucleolin to the nucleoplasm. Following expression of nonreplicating HDV RNAs, deltaAg moved to the nucleoplasm, but nucleolin was unchanged. When deltaAg was expressed along with replicating HDV RNA, it was found predominantly in the nucleoplasm along with Pol II. This localization was insensitive to inhibitors of HDV replication, suggesting that the majority of deltaAg in the nucleoplasm reflects ribonucleoprotein accumulation rather than ongoing transcription. An additional approach was to reevaluate several forms of deltaAg altered at specific locations considered to be essential for protein function. These studies provide evidence that deltaAg does not interact directly with either Pol II or nucleolin and that forms of deltaAg which support replication are also capable of prior nucleolar transit.
...
PMID:Intracellular localization of hepatitis delta virus proteins in the presence and absence of viral RNA accumulation. 1936 24

RBMY is a male germline RNA binding protein and potential alternative splicing regulator, but the lack of a convenient biological system has made its cellular functions elusive. We found that human RBMY fused to green fluorescent protein was strictly nuclear in transfected cells, but spatially enriched in areas around nuclear speckles with some components of the exon junction complex (EJC). Human RBMY (hRBMY) and the EJC components Magoh and Y14 also physically interacted but, unlike these two proteins, hRBMY protein did not shuttle to the cytoplasm. In addition, it relocalised into nucleolar caps after inhibition of RNA polymerase II transcription. Protein interactions were also detected between RBMY and splicing factors 9G8 and transformer-2 protein homolog beta (Tra2-beta), mediated by multiple regions of the RBMY protein that contain serine/arginine-rich dipeptides, but not by the single region lacking such dipeptides. These interactions modulated the splicing of several pre-mRNAs regulated by 9G8 and Tra2-beta. Importantly, ectopic expression of hRBMY stimulated the inclusion of a testis-enriched exon from the Acinus gene, whereas 9G8 and Tra2-beta repressed this exon. We propose that hRBMY associates with regions of the nucleus enriched in nascent RNA and participates in the regulation of specific splicing events in the germline by modulating the activity of constitutively expressed splicing factors.
...
PMID:Human RBMY regulates germline-specific splicing events by modulating the function of the serine/arginine-rich proteins 9G8 and Tra2-{beta}. 2001 65


1 2 Next >>

---