Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC-II deficiency is recognized by defects in components of the RFX complex or CIITA. In this study, we have characterized at the molecular level the putative defect in MHC-II regulatory factors of a recently identified MHC-II deficiency patient (FGK). We found that this patient lacked detectable levels of mRNA and protein of the RFX complex subunit RFXAP. It was subsequently established that the RFXAP gene in FGK differed from wild type RFXAP by a homozygous 75bp insertion in the 5'-UTR, which impaired the activity of the FGK RFXAP promoter. The transcriptional silent state of RFXAP correlated with reduced recruitment of RNA polymerase II to FGK RFXAP chromatin. Together, this insertion in the promoter region represents a novel type of MHC-II gene silencing in MHC-II deficiency patients.
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PMID:Transcriptional silencing of RFXAP in MHC class II-deficiency. 1833 11

The sigmas subunit of RNA polymerase is a central regulator which governs the expression of a host of stationary phase-induced and osmotically regulated genes in Gram-negative bacteria. The Pseudomonas putida rpoS gene is transcribed as a monocistronic rpoS mRNA with a 368 nucleotide-long 5' untranslated region (5' UTR). In this study, we investigate the posttranscriptional control of RpoS synthesis using rpoS-lacZ transcriptional and translational fusions consisting of the native promoter and deletions of 5' UTR or insertion into UTR. The differing activity of constructed translational fusions strongly indicated that the 5' UTR is involved in the translational regulation of RpoS expression in the stationary phase. The results obtained herein demonstrated that the structure of UTR performs an important function in the translational regulation of the rpoS gene.
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PMID:5' Untranslated region of the Pseudomonas putida WCS358 stationary phase sigma factor rpoS mRNA is involved in RpoS translational regulation. 1833 94

Picornaviruses are a class of RNA viruses with a single-stranded genome in positive orientation. Since the prospects of treatment are limited, we employ RNA interference (RNAi) as an antiviral tool to inhibit different picornaviruses. We identified small interfering RNAs (siRNAs) against the 3D RNA dependent RNA polymerase of coxsackievirus B3 that were capable of efficiently inhibiting the virus. Targeting of the conserved 5' UTR of the virus turned out to be a challenging task since stable structures of this region are detrimental to silencing. We developed a rational strategy to solve this problem and found an siRNA containing locked nucleic acids (LNAs) to possess high antiviral potency. To analyse the mechanism of virus inhibition in more detail, LNAs were incorporated into the siRNA to inactivate either of the siRNA strands. These experiments clearly revealed that only the genomic plus-strand but not the intermediary synthesised minus-strand can be targeted by siRNAs. Furthermore, siRNAs were employed to silence the virus receptor on the host cell and thus prevent viral spread.
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PMID:Inhibition of picornaviruses by means of RNA interference. 1877 54

RNA interference (RNAi) has been used as an effective antiviral strategy for its specific silencing of viral gene expression in mammalian cells. In this study, shRNA targeting two regions of Foot and Mouth Disease Virus (FMDV) i.e. 3D and 5'UTR which are very essential in virus replication were evaluated. The constructs were made using h7K RNA polymerase III promoter. We investigated in vivo inhibitory effect of shRNA on FMDV replication in BHK-21 cells and guinea pigs. The results showed that transfection of 3D shRNA could reduce virus growth by three folds when cells were challenged with 10(2) TCID(50) of FMDV. Pretreated guinea pigs with 3DshRNA were protected 80% with 10(3) GPID(50) of FMDV. As a first report in guinea pigs which are recognized animal model for FMD vaccine potency testing, the study suggests that shRNA could be a viable therapeutic approach to control severity of FMD infection and spread.
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PMID:The plasmid constructs producing shRNA corresponding to the conserved 3D polymerase of Foot and Mouth Disease virus protects guinea pigs against challenge virus. 1881 Jun 49

Positive transcription elongation factor b (P-TEFb) is an important transcriptional regulator which controls 70-80% of RNA polymerase II transcription. It has been reported that the human I-mfa (inhibitor of MyoD family a) domain-containing protein (HIC) interacts with P-TEFb and that expression of HIC cDNA stimulates P-TEFb-dependent transcription. Interestingly, our recent study shows that transcriptional stimulation by HIC is predominately due to the 3' untranslated region (3'UTR) of HIC mRNA rather than its coding region. In this report, we investigate the effects of HIC 3'UTR on recombinant protein expression in mammalian cells. In transient transfections, overexpression of HIC 3'UTR stimulates transgene expression in several mammalian cell lines and significantly increases the production of human erythropoietin and interferon-gamma in Chinese hamster ovary (CHO) cells. This is the first report that demonstrates the improvement of expression of biopharmaceutical proteins by overexpressing a non-coding 3'UTR in CHO cells.
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PMID:The 3'UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells. 1904 12

A cotton (Gossypium hirsutum L.) genomic clone encompassing a 17.9-kb DNA fragment was found to contain a delta-12 fatty acid desaturase gene (designated FAD2-4). The FAD2-4 open reading frame has 1,155bp and is uninterrupted, encoding a conceptual FAD2-4 polypeptide of 384 amino acids that has 98% identity with the cotton FAD2-3 polypeptide. The FAD2-4 gene has a single intron of 2,780 bp in its 5'-untranslated region (5'-UTR). The 3'-flanking regions and 5'-UTR introns in the FAD2-4 and FAD2-3 genes are quite different, indicating that the genes might be paralogs in the cotton genome. Reverse transcriptase (RT)-PCR analysis indicated that the FAD2-4 and FAD2-3 genes were expressed in all tissues examined, including seeds, seedling tissues, young and mature leaves, roots, stems, developing flower buds, and ovule fibers. These constitutive patterns of expression were notably different from that of the FAD2-1 gene, which was restricted to seeds and developing flower buds, or to the expression of a newly-identified FAD2-2 gene isoform, which was barely detectable in roots, hypocotyls, stems, and fibers, but was expressed in all other tissues. The FAD2-4 coding region was expressed in yeast and shown to encode a functional delta-12 desaturase, converting oleic acid (C18:1) to linoleic acid (C18:2) in recombinant yeast cells. In addition, both the FAD2-4 and the FAD2-3 genes were transferred into the Arabidopsis thaliana fad2-1 mutant background where they effectively restored wild type fatty acid composition and growth characteristics. Finally, the cotton FAD2-4 green fluorescent protein (GFP) fusion polypeptide appeared to be localized in the endomembrane system of transgenic Arabidopsis plants in the complemented fad2-1 mutant background, supporting a functional ER location for the cotton FAD2-4 polypeptide in this heterologous plant system. Thus, a new functional member of the FAD2 gene family in cotton has been characterized, indicating a complex regulation of membrane lipid desaturation in this important fiber/oilseed crop.
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PMID:Identification and expression of a new delta-12 fatty acid desaturase (FAD2-4) gene in upland cotton and its functional expression in yeast and Arabidopsis thaliana plants. 1921 93

Riboswitches encompass messenger ribonucleic acid transcripts that sense the concentration of small molecule metabolites through binding the target compound and then control the expression of metabolite-related genes in response to the metabolite concentration. While much of the riboswitch-related research has focused on the remarkable ability of different aptamer domains to adopt the intricate structures required to bind a spectrum of biological metabolites with high affinity and specificity, less attention has been paid to the mechanism of riboswitch action. Specifically, the genetic control element of the riboswitch, known as the expression platform, must function cotranscriptionally in the case of transcription termination-controlled riboswitches. By correlating the transcriptional kinetics of the entire switch and the kinetics and thermodynamics of metabolite binding of the aptamer domain, it was found that the FMN-binding riboswitch in the 5' UTR of the Bacillus subtilis ribGBAHT operon functions as a kinetically controlled genetic switch chiefly dependent upon transcriptional pausing and the concentration of the target metabolite. This study has emphasized the importance of studying the switch in its entirety and in the context of an actively transcribing RNA polymerase. Herein I will describe the study of the kinetics of riboswitch transcription and the proposed mechanism for the transcription termination-associated riboswitch control of riboflavin-related genes.
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PMID:Kinetics of riboswitch regulation studied by in vitro transcription. 1938 52

Cancer is currently a major public health problem and, as such, emerging research is making significant progress in identifying major players in its biology. One recent topic of interest involves microRNAs (miRNAs) which are small, non-coding RNA molecules that inhibit gene expression post-transcriptionally. They accomplish this by binding to the 3' untranslated region (3'UTR) of target messengerRNA (mRNA), resulting in either their degradation or inhibition of translation, depending on the degree of complementary base pairing. They are transcribed by RNA polymerase II and are formed into mature miRNAs via two steps, each catalyzed by a different ribonuclease III (RNaseIII). Cross-species comparisons demonstrate that miRNAs are evolutionarily conserved and play important roles in a wide array of normal biological processes. Importantly, aberrant miRNA expression is correlated with human disease, especially in the development of cancer. Recent research has identified targets and functions of miRNAs, illustrating that some are oncogenic in nature while others show tumor suppressor activity. The miRNAs have also been characterized as having high potential in the clinical arena and, as such, have been a target for exploitation toward cancer therapy. Not only has it been shown that miRNA expression profiles may prove useful as diagnostic and prognostic markers in cancer, various miRNA-based therapies show promise as well. It is anticipated that further research will elucidate the benefits of using miRNAs as clinical agents in the battle against cancer and other chronic diseases.
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PMID:MicroRNA and Cancer: Tiny Molecules with Major Implications. 1944 Apr 50

Rna15 is a core subunit of cleavage factor IA (CFIA), an essential transcriptional 3'-end processing factor from Saccharomyces cerevisiae. CFIA is required for polyA site selection/cleavage targeting RNA sequences that surround polyadenylation sites in the 3'-UTR of RNA polymerase-II transcripts. RNA recognition by CFIA is mediated by an RNA recognition motif (RRM) contained in the Rna15 subunit of the complex. We show here that Rna15 has a strong and unexpected preference for GU containing RNAs and reveal the molecular basis for a base selectivity mechanism that accommodates G or U but discriminates against C and A bases. This mode of base selectivity is rather different to that observed in other RRM-RNA structures and is structurally conserved in CstF64, the mammalian counterpart of Rna15. Our observations provide evidence for a highly conserved mechanism of base recognition amongst the 3'-end processing complexes that interact with the U-rich or U/G-rich elements at 3'-end cleavage/polyadenylation sites.
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PMID:Structure of the Rna15 RRM-RNA complex reveals the molecular basis of GU specificity in transcriptional 3'-end processing factors. 2009 54

Short interspersed elements (SINEs), which are mainly composed of Bm1, are abundant in the domesticated silkworm. A 294 bp novel SINE family, designated as BmSE, was identified by mining the database of the complete Bombyx mori genome. A representational BmSE element is flanked by an 11 bp target site duplication sequence posterior poly (A) at the 3' end and has the sequence motifs of an internal promoter of RNA polymerase III, which are similar to that of Bm1. The repetitive elements of BmSE are widely distributed in all 28 chromosomes of the genome and share the common (ATTT) repeats at the ends. GC-content distribution shows that BmSE tends to accumulate preferably in the region of higher AT content than that of Bm1. A high proportion of the BmSEs are mapped to the coding sequence introns, whereas several elements are also present in the UTR of some transcripts, indicating that BmSEs are indeed exonized with UTRs. Of the 615 identified structural variants (SVs) of BmSE among the 40 domesticated and wild silkworms, only 230 SVs were found in the domesticated silkworms, indicating that many recent SV events of BmSE occurred after domestication, which was probably due to its mobilization. Our analysis might assist in developing BmSE as a potential marker and in understanding the evolutionary roles of SINEs in the domesticated silkworm.
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PMID:BmSE, a SINE family with 3' ends of (ATTT) repeats in domesticated silkworm (Bombyx mori). 2022 46


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