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Results for “RNA Regulation”

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At least 217 records · Page 12Linked to original sources
PubMed1977

Regulation of RNA polymerase II activity in alpha-amanitin-resistant CHO hybrid cells.

CHO hybrid cell lines obtained by fusing cells of wild-type sensitivity to alpha-amanitin with mutant cells containing RNA polymerase II activity resistant to alpha-amanitin have both sensitive (wild-type) and resistant forms of RNA polymerase II. When these hybrids were grown in medium containing alpha-amanitin, the sensitive form of polymerase II was inactivated, and the activity resistant to alpha-amanitin increased proportionally. The total polymerase II activity level therefore remained constant. This regulation of RNA polymerase II activity occurred independently of that of RNA polymerase I and was similar to that observed previously in the alpha-amanitin-resistant rat myoblast mutant clone Ama102 (Somers, Pearson, and Ingles, 1975a). A sensitive radioimmunoassay was developed to quantitate the total mass of RNA polymerase II enzyme. Under conditions of regulation of the enzymatic activity when hybrids grown in alpha-amanitin exhibited a 2-3 fold increase in the activity of the alpha-amanitin-resistant enzyme, no major change in the enzyme mass was detected immunologically. However, quantitation of the alpha-amanitin-inactivated polymerase II of wild-type sensitivity by 3H-amanitin binding indicated that the loss of its enzymic activity was accompanied by a loss of 3H-amanitin binding capacity in the cell lysates. All these results taken together indicate that a mechanism for regulating the intracellular level of RNA polymerase II exists and that it involves changes in the concentration of enzyme.

Amanitins↗
PubMed2004

6S RNA function enhances long-term cell survival.

6S RNA was identified in Escherichia coli >30 years ago, but the physiological role of this RNA has remained elusive. Here, we demonstrate that 6S RNA-deficient cells are at a disadvantage for survival in stationary phase, a time when 6S RNA regulates transcription. Growth defects were most apparent as a decrease in the competitive fitness of cells lacking 6S RNA. To decipher the molecular mechanisms underlying the growth defects, we have expanded studies of 6S RNA effects on transcription. 6S RNA inhibition of sigma(70)-dependent transcription was not ubiquitous, in spite of the fact that the vast majority of sigma(70)-RNA polymerase is bound by 6S RNA during stationary phase. The sigma(70)-dependent promoters inhibited by 6S RNA contain an extended -10 promoter element, suggesting that this feature may define a class of 6S RNA-regulated genes. We also discovered a secondary effect of 6S RNA in the activation of sigma(S)-dependent transcription at several promoters. We conclude that 6S RNA regulation of both sigma(70) and sigma(S) activities contributes to increased cell persistence during nutrient deprivation.

Bacterial Proteins↗
PubMed1979

The regulation of RNA synthesis in yeast IV. Synthesis of double-stranded RNA.

A study has been made of the regulation of the synthesis of Pl double-stranded (ds) RNA, the genome of the yeast virus-like particle. When yeast protein synthesis is prevented by starvation for a required amino acid or by addition of cycloheximide, the rate of Pl dsRNA synthesis is reduced markedly. During nitrogen starvation the synthesis of Pl dsRNA persists but is accompanied by the degradation of pre-existing molecules. This degradation appears to require the induction of new enzymes and it is likely that the breakdown products are used to enable the cell to complete its division cycle. However, all of the copies of the VLP genome are not degraded in this process, some are conserved and can replenish the amount of Pl dsRNA on return to growth conditions. The controls which must operate on Pl dsRNA synthesis are discussed and compared with those exerted on nuclear RNA synthesis in yeast.

Cell Division↗
PubMed1986

Regulation of RNA metabolism in relation to insulin production and oxidative metabolism in mouse pancreatic islets in vitro.

This study was undertaken to investigate the long-term effects of different substrates, in particular glucose, on the regulation of islet RNA metabolism and the relationship of this regulation to the metabolism and insulin production of the islet B-cell. For this purpose collagenase-isolated mouse islets were used either in the fresh state or after culture for 2 or 5 days in RPMI 1640 plus 10% calf serum supplemented with various test compounds. Islets cultured with 16.7 mM glucose contained more RNA than those cultured with 3.3 mM glucose. Culture of islets in glucose at low concentrations inhibited glucose-stimulated RNA synthesis and this inhibitory effect was reversed by prolonged exposure to high glucose concentrations. Culture with 10 mM leucine and 3.3 mM glucose or with 10 mM 2-ketoisocaproate and 3.3 mM glucose increased the total RNA content of islets as compared to that of islets cultured with 3.3 mM glucose alone. Islets cultured with 5 mM theophylline maintained a high RNA content in the presence of 3.3 mM glucose. Theophylline also increased the islet RNA content when added together with 16.7 mM glucose, as compared to 16.7 mM glucose alone. Theophylline probably exerted this effect by decreasing the rate of RNA degradation. Changes in islet RNA metabolism showed a close correlation to changes in islet total protein biosynthesis, whereas islet (pro)insulin biosynthesis and insulin release exhibited different glucose-dependency patterns. The response of islet oxygen uptake to glucose was similar to that of islet RNA and protein biosynthesis. It is concluded that the RNA content of the pancreatic islets is controlled at the levels of both synthesis and degradation. Glucose stimulates the RNA synthesis and inhibits its degradation. Moreover, the results suggest that regulation of RNA synthesis may be mediated through islet metabolic fluxes and the cAMP system.

Animals↗
PubMed2004

Validation of antibacterial mechanism of action using regulated antisense RNA expression in Staphylococcus aureus.

Validation of antibiotic mode of action in whole bacterial cells is a key step for antibiotic drug discovery. In this study, one potential drug target, enoyl-acyl carrier protein reductase (FabI), an essential enzyme in the fatty acid biosynthesis pathway, was used to evaluate the feasibility of using a regulated antisense RNA interference approach to determine antibiotic mode of action. Antisense isogenic strains expressing antisense RNA to fabI were created using a tetracycline-regulated vector in Staphylococcus aureus. We demonstrated that down-regulation of FabI expression by induction of fabI antisense RNA induces a conditional lethal phenotype. In contrast, partial down-regulation gives a viable cell with a significant increase in sensitivity to FabI-specific inhibitors (i.e., a sensitized phenotype). More importantly, the mode of action for novel FabI inhibitors has been confirmed using this genetic approach in whole cell assay. These results indicate that controlled antisense technology provides a robust tool for defining and tracking the mode of action of novel antibacterial agents.

Anti-Bacterial Agents↗
PubMed1991

RNA polymerase: regulation of transcript elongation and termination.

Expanded interest in studying the mechanisms of elongation and termination during transcription has come as a result of several recent findings that highlight the importance of the regulation of these processes in human health. Several cellular proto-oncogenes contain regulated blocks to elongation (1), and the human immunodeficiency viruses also control gene expression in part by regulating the efficiency of elongation in response to the trans-activating protein, TAT (2). This review considers these recent findings and compares potential mechanisms of regulation used by prokaryotic and eukaryotic RNA polymerases during elongation and termination. In all these systems, many of the detailed mechanisms of transcription elongation and termination are still to be defined; however, we have tried to group examples that may share some common regulatory elements into simplified categories.

Animals↗
PubMed2000

Promoter-proximal pausing on the hsp70 promoter in Drosophila melanogaster depends on the upstream regulator.

RNA polymerase II pauses in the promoter-proximal region of many genes during transcription. In the case of the hsp70 promoter from Drosophila melanogaster, this pause is long-lived and occurs even when the gene is not induced. Paused polymerase escapes during heat shock when the transcriptional activator heat shock factor associates with the promoter. However, pausing is still evident, especially when induction is at an intermediate level. Yeast Gal4 protein (Gal4p) will induce transcription of the hsp70 promoter in Drosophila when binding sites for Gal4p are positioned upstream from the hsp70 TATA element. To further our understanding of promoter-proximal pausing, we have analyzed the effect of Gal4p on promoter-proximal pausing in salivary glands of Drosophila larvae. Using permanganate genomic footprinting, we observed that various levels of Gal4p induction resulted in an even distribution of RNA polymerase throughout the first 76 nucleotides of the transcribed region. In contrast, promoter-proximal pausing still occurs on endogenous and transgenic hsp70 promoters in salivary glands when these promoters are induced by heat shock. We also determined that mutations introduced into the region where the polymerase pauses do not inhibit pausing in a cell-free system. Taken together, these results indicate that promoter-proximal pausing is dictated by the regulatory proteins interacting upstream from the core promoter region.

Animals↗
PubMed1998

RNA-mediated regulation of Bc1-2 and cyclin 'D' genes in human platelets.

The aim of this study was to understand the RNA-mediated regulation of genes coding for Bc1-2 and cyclin 'D'. Evidence was provided that these genes are regulated by receptor-C(k)-dependent signalling in human platelets. Further experiments to resolve the mechanism through which receptor-C(k) regulates these genes revealed that receptor-C(k)-dependent signalling is involved in the cleavage of a 125-kDa protein present in endoplasmic reticulum, resulting in generation of a 47-kDa factor that has affinity for a genomic sterol regulatory element as well as the platelet mRNA pool. Based upon these findings we propose a receptor-C(k) dependent signalling pathway for the regulation of Bc1-2 and cyclin 'D' genes at the post-transcriptional level.

Journal Article↗
PubMed2003

Sigma28 RNA polymerase regulates hctB, a late developmental gene in Chlamydia.

Chlamydia is predicted to encode two alternative sigma factors that could provide a mechanism for the regulation of gene expression via alternative forms of RNA polymerase. We have demonstrated that sigma 28, one of these alternative sigma factors, is transcriptionally active. Chlamydial sigma 28 RNA polymerase was reconstituted from recombinant sigma 28 protein and core enzyme that was biochemically isolated from chlamydiae. In an in vitro transcription assay, sigma 28 RNA polymerase transcribed the hctB promoter in a sigma 28-dependent manner. Transcription by sigma 28 RNA polymerase was salt tolerant compared with transcription by sigma 66 RNA polymerase, the major form of chlamydial RNA polymerase. As hctB encodes a histone-like protein that is only expressed late in the developmental cycle, our results suggest that sigma 28 RNA polymerase has a role in the regulation of late gene expression in Chlamydia.

Bacterial Proteins↗
PubMed1993

Regulation of RNA polymerase II transcription.

Transcription initiation plays a central role in the regulation of gene expression. Exciting developments in the last year have furthered our understanding of the interactions between general transcription factors and how these factors respond to modulators of transcription.

Animals↗
PubMed1969

Nucleoside triphosphate pools and the regulation of RNA synthesis in E. coli.

Amino acid starvation of "stringent RNA control" (RC(str)) strains of Escherichia coli (E. coli) results in the cessation of net protein and net RNA synthesis, whereas "relaxed RNA control" (RC(rel)) strains continue net RNA synthesis under the same conditions of amino acid starvation. This report tests further the hypothesis that net RNA synthesis is markedly reduced during amino acid starvation of RC(str) strains as a result of reduction in the supply of substrates of the RNA polymerase. Bacterial ribonucleoside triphosphate pool levels were measured before and after the arrest of protein synthesis in RC(str) and RC(rel) strains. Protein synthesis was inhibited either by addition of trimethoprim to the medium or by the use of a mutant having a temperature-sensitive valyl-tRNA synthetase. The ribonucleoside triphosphate pool levels do not decline significantly during inhibition of protein synthesis in RC(str) strains under either condition, and there is no apparent correlation between the measured pool levels and the residual rate of net RNA synthesis in RC(str) and RC(rel) strains. Thus, these data argue against the hypothesis that the regulation of RNA synthesis is mediated by the availability of substrates of the RNA polymerase.

Adenine Nucleotides↗
PubMed2006

A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.

Recent advances in genome-wide analysis of alternative splicing indicate that extensive alternative RNA processing is associated with many proteins that play important roles in the nervous system. Although differential splicing and polyadenylation make significant contributions to the complexity of the nervous system, our understanding of the regulatory mechanisms underlying the neuron-specific pathways is very limited. Mammalian neuron-specific embryonic lethal abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding proteins implicated in neuronal differentiation and maintenance. It has been established that Hu proteins increase expression of proteins associated with neuronal function by up-regulating mRNA stability and/or translation in the cytoplasm. We report here a novel function of these proteins as RNA processing regulators in the nucleus. We further elucidate the underlying mechanism of this regulation. We show that in neuron-like cells, Hu proteins block the activity of TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA processing. These studies define not only the first neuron-specific regulator of the calcitonin/CGRP system but also the first nuclear function of Hu proteins.

Alternative Splicing↗
PubMed1997

A transforming growth factor-beta regulable RNA-binding protein interacts specifically with germline Ig alpha transcripts.

Isotype switching is presaged by the transcriptional activation of the heavy chain class gene (CH) to which recombination will occur. As a result, mRNA or germline transcripts from the unrearranged gene accumulate in the cytoplasm. Previous studies demonstrated that transforming growth factor (TGF)-beta stimulated isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated murine B cells and increased the stability of C alpha mRNAs. The present study demonstrates that LPS-stimulated B cells express a 45 kDa protein, I alpha BP, that specifically binds to germline alpha transcripts. Following addition of TGF-beta, the binding activity of this protein is significantly reduced. The identification of a cytokine regulable RNA-binding protein that interacts with germline transcripts supports the idea that these transcripts are involved in recombination and raises the possibility that RNA-protein interactions play a role in regulating isotype switching.

Animals↗
PubMed1999

Regulation of RNA polymerase I transcription in yeast and vertebrates.

This article focuses on what is currently known about the regulation of transcription by RNA polymerase I (pol I) in eukaryotic organisms at opposite ends of the evolutionary spectrum--a yeast, Saccharomyces cerevisiae, and vertebrates, including mice, frogs, and man. Contemporary studies that have defined the DNA sequence elements are described, as well as the majority of the basal transcription factors essential for pol I transcription. Situations in which pol I transcription is known to be regulated are reviewed and possible regulatory mechanisms are critically discussed. Some aspects of basal pol I transcription machinery appear to have been conserved from fungi to vertebrates, but other aspects have evolved, perhaps to meet the needs of a metazoan organism. Different parts of the pol I transcription machinery are regulatory targets depending on different physiological stimuli. This suggests that multiple signaling pathways may also be involved. The involvement of ribosomal genes and their transcripts in events such as mitosis, cancer, and aging is discussed.

Animals↗
PubMed2000

A conserved cis-acting element in the parathyroid hormone 3'-untranslated region is sufficient for regulation of RNA stability by calcium and phosphate.

Calcium and phosphate regulate parathyroid hormone (PTH) gene expression post-transcriptionally by changes in protein-PTH mRNA 3'-untranslated region (UTR) interactions, which determine PTH mRNA stability. We have identified the protein binding sequence in the PTH mRNA 3'-UTR and determined its functionality. The protein-binding element was identified by binding, competition, and antisense oligonucleotide interference. The sequence was preserved among species suggesting its importance. To study its functionality in the context of another RNA, a 63-base pair cDNA PTH sequence was fused to the growth hormone (GH) gene. There is no parathyroid (PT) cell line and therefore an in vitro degradation assay was used to determine the stability of transcripts for PTH, GH, and a chimeric GH-PTH 63 nucleotides with PT cytosolic proteins. The full-length PTH transcript was stabilized by PT proteins from rats fed a low calcium diet and destabilized by proteins from rats fed a low phosphate diet, correlating with PTH mRNA levels in vivo. These PT proteins did not affect the native GH transcript. However, the chimeric GH transcript was stabilized by low calcium PT proteins and destabilized by low phosphate PT proteins, similar to the PTH full-length transcript. Therefore, we have identified a PTH RNA-protein binding region and shown that it is sufficient to confer responsiveness to calcium and phosphate in a reporter gene. This defined element in the PTH mRNA 3'-UTR is necessary and sufficient for the regulation of PTH mRNA stability by calcium and phosphate.

3' Untranslated Regions↗
PubMed2001

The amino acid sequence of a plastid protein is developmentally regulated by RNA editing.

RNA editing in plant organelles post-transcriptionally alters single nucleotides by C-to-U or U-to-C conversions at highly specific sites. Plant editing is generally viewed as a repair mechanism acting at the transcript level by restoring conserved amino acid residues. Here we report that an editing reaction within the ndhB transcript (encoding a plastid NAD(P)H dehydrogenase subunit) is strictly dependent on active photosynthesis. Employing non-photosynthetic mutants, we show that in the absence of photosynthesis, the site remains unedited, whereas it is fully edited when the photosynthetic apparatus is intact. Moreover, the site also remains unedited during the etiolated stage of seedling development, suggesting that two different NdhB proteins are synthesized under photosynthetic versus non-photosynthetic conditions. This is the first case where RNA editing in plants appears to regulate gene expression qualitatively, resulting in the production of two different proteins from one and the same gene in a developmental stage-dependent manner.

Base Sequence↗
PubMed2001

Identification of a novel AU-Rich element in the 3' untranslated region of epidermal growth factor receptor mRNA that is the target for regulated RNA-binding proteins.

The epidermal growth factor receptor (EGF-R) plays an important role in the growth and progression of estrogen receptor-negative human breast cancers. EGF binds with high affinity to the EGF-R and activates a variety of second messenger pathways that affect cellular proliferation. However, the underlying mechanisms involved in the regulation of EGF-R expression in breast cancer cells are yet to be described. Here we show that the EGF-induced upregulation of EGF-R mRNA in two human breast cancer cell lines that overexpress EGF-R (MDA-MB-468 and BT-20) is accompanied by stabilization (>2-fold) of EGF-R mRNA. Transient transfections using a luciferase reporter identified a novel EGF-regulated approximately 260-nucleotide (nt) cis-acting element in the 3' untranslated region (3'-UTR) of EGF-R mRNA. This cis element contains two distinct AU-rich sequences (~75 nt), EGF-R1A with two AUUUA pentamers and EGF-R2A with two AUUUUUA extended pentamers. Each independently regulated the mRNA stability of the heterologous reporter. Analysis of mutants of the EGF-R2A AU-rich sequence demonstrated a role for the 3' extended pentamer in regulating basal turnover. RNA gel shift analysis identified cytoplasmic proteins (~55 to 80 kDa) from breast cancer cells that bound specifically to the EGF-R1A and EGF-R2A cis-acting elements and whose binding activity was rapidly downregulated by EGF and phorbol esters. RNA gel shift analysis of EGF-R2A mutants identified a role for the 3' extended AU pentamer, but not the 5' extended pentamer, in binding proteins. These EGF-R mRNA-binding proteins were present in multiple human breast and prostate cancer cell lines. In summary, these data demonstrate a central role for mRNA stabilization in the control of EGF-R gene expression in breast cancer cells. EGF-R mRNA contains a novel complex AU-rich 260-nt cis-acting destabilizing element in the 3'-UTR that is bound by specific and EGF-regulated trans-acting factors. Furthermore, the 3' extended AU pentamer of EGF-R2A plays a central role in regulating EGF-R mRNA stability and the binding of specific RNA-binding proteins. These findings suggest that regulated RNA-protein interactions involving this novel cis-acting element will be a major determinant of EGF-R mRNA stability.

3' Untranslated Regions↗
PubMed1997

RNA-mediated regulation of Receptor-Ck gene in human platelets.

The study addressed to understand the regulation of Receptor-'Ck' gene at the translational level revealed that exogenous cholesterol has the inherent capacity to regulate the endogenous synthesis of Receptor-'Ck' by initiating intracellular targeting of the Receptor-'Ck' to the mRNP pool within human platelets and this effect could be reversed when the platelets were incubated with cholesterol coupled with either dB cAMP or dB cGMP. Based upon these observations, we propose that Receptor-'Ck' initiated signalling, which involves second messengers like PA, cAMP and cGMP, may be responsible for the autoregulation of Receptor-'Ck' gene expression at the translational level.

Blood Platelets↗