Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RNA Regulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed2000

Hormonal regulation of mRNA stability and RNA-protein interactions in the pituitary.

Regulating gene expression from DNA to protein is a complex multistage process with multiple control mechanisms. Transcriptional regulation has been considered the major control point of protein production in eukaryotic cells; however, there is growing evidence of pivotal posttranscriptional regulation for many genes. This has prompted extensive investigations to elucidate the mechanisms controlling RNA processing, mRNA nuclear export and localization, mRNA stability and turnover, in addition to translational rates and posttranslational events. The regulation of mRNA stability has emerged as a critical control step in determining the cellular mRNA level, with individual mRNAs displaying a wide range of stability that has been linked to discrete sequence elements and specific RNA-protein interactions. This review will focus on current knowledge of the determinants of mRNA stability and RNA-protein interactions in the pituitary. This field is rapidly expanding with the identification of regulated cis-acting stability-modifying elements within many mRNAs, and the cloning and characterization of trans-acting proteins that specifically bind to their cognate cis elements. We will present evidence for regulation of multiple pituitary genes at the level of mRNA stability and some examples of the emerging data characterizing RNA-protein interactions.

Animals↗
PubMed1991

Studies on the regulation of influenza virus RNA replication: a differential inhibition of the synthesis of vRNA segments in shift-up experiments with ts mutants.

The regulation of influenza virus vRNA synthesis in the course of the reproduction cycle was studied with the use of a series of ts mutants in shift-up experiments. The synthesis of vRNA segments was registered by means of polyacrylamide gel electrophoresis of nucleocapsid-associated RNA isolated from the infected cells labelled with [3H]uridine after the shift-up to a semi-permissive temperature. Each mutant exhibited a specific differential pattern of vRNA synthesis inhibition after the shift-up. The most affected segments were either vRNA 4, vRNAs 4 and 7, or vRNAs 4, 6, and 7 in cells infected, respectively, with ts mutants C15 (ts lesion in PB1 gene), C45 (ts lesion in PA gene) and CmN3 (ts lesion in NS gene). The synthesis of vRNAs 1, 2, and 3 was relatively resistant to the shift-up in the cells infected with C15 or C45 and more sensitive in the cells infected with C44 (ts lesion in PB2 gene) or CmN3. The replication of the "early" genes (vRNAs 5 and 8) was generally least affected by the shift-up. The results are discussed in connection with the "early-late" transition of vRNA synthesis pattern in the course of infection.

Animals↗
PubMed1996

Cell cycle regulation of BRCA1 messenger RNA in human breast epithelial cells.

BRCA1 was originally isolated as a gene that conferred susceptibility to early-onset familial breast and ovarian cancers. The function and regulation of this gene is presently unknown. Northern blot analyses using probes that recognize different regions of the BRCA1 cDNA revealed the presence of at least two distinct mRNA species. In synchronized normal and immortalized human mammary epithelial cells, BRCA1 mRNA levels were high in exponentially growing populations, decreased upon growth factor withdrawal, and subsequently increased again in late G1 just prior to S-phase entry. BRCA1 mRNA levels were found to be dramatically reduced in senescent normal human mammary epithelial cells and in normal human mammary epithelial cells treated with transforming growth factor beta 1. When considered together, these data indicate that expression of BRCA1 mRNA is highly sensitive to changes in growth conditions in vitro. BRCA1 proteins with apparent molecular weights of M(r) 210,000, 185,000, 160,000, 135,000, and 85,000, respectively, were detected at varying levels in all breast epithelial cells examined. Further molecular characterization of the nature and function of the different BRCA1 mRNAs and proteins should increase our understanding of this gene in the etiology of human breast cancers.

Breast↗
PubMed1990

How Escherichia coli RNA polymerase can negatively regulate transcription from a constitutive promoter.

We previously described the structures and functions of specific complexes between the bla promoter from Tn3 (present in pBR322) and RNA polymerase (RNAP), showing that, at excess RNAP, complexes can form in which one or two RNAPs bind to the same promoter (1:1 and 2:1 complexes) (Duval-Valentin and Ehrlich, 1988). We report here that the 2:1 complex cannot be detected below 25 degrees C; above that temperature, a 1:1 complex forms at a rate one order of magnitude faster than that of the 2:1 complex, and above 30 degrees C, the amounts of both species become equal for RNAP/promoter ratio r30 less than or equal to r less than or equal to 70. The 2:1 complex decays back to a 1:1 complex losing the last RNAP at a rate about three times that of the 1:1 complex decay. Functional assays of the complexes formed at excess RNAP show that both 1:1 and 2:1 complexes are immediately and permanently inhibited, even when the promoters are pre-incubated with ribonucleotide selections potentially enabling entrance into abortive cycling or formation of a stressed complex. We conclude that the inhibition step probably takes place in the complex formation pathway between RPi and RPo, at a novel stable intermediate isomer, RPj, formed above 25 degrees C. A possible mechanism of formation of the 2:1 complex is outlined. In vivo studies, in which r was modified by varying the bacterial growth rate, show a reduction of bla expression as r values are upshifted, specific to the bla promoter from Tn3.

DNA-Directed RNA Polymerases↗
PubMed1997

RNA-binding proteins as regulators of gene expression.

A plethora of post-transcriptional mechanisms are involved in essential steps in the pathway of genetic information expression in eukaryotes. These processes are specified by cis-acting signals on RNAs and are mediated by specific trans-acting factors, including RNA-binding proteins and small complementary RNAs. Recent information has begun to define the molecular mechanisms by which RNA-binding proteins recognize specific RNA sequences and influence the processing and function of RNA molecules.

Amino Acid Sequence↗
PubMed1990

Regulation of sex-specific RNA splicing at the Drosophila doublesex gene: cis-acting mutations in exon sequences alter sex-specific RNA splicing patterns.

Sex-specific alternative RNA splicing of the doublesex (dsx) pre-mRNA results in sex-specific polypeptides that regulate both male and female somatic sexual differentiation in Drosophila melanogaster. We have molecularly characterized a class of dsx mutations that act in cis to disrupt the regulation of dsx RNA processing, causing the dsx pre-mRNA to be spliced in the male-specific pattern regardless of the chromosomal sex of the fly. These dsx mutations are associated with rearrangements in the female-specific exon just 3' to the female-specific splice acceptor. The mutations do not affect the female-specific splice sites or intron that are identical to wild-type sequences. These results indicate that sequences in the female-specific exon are important for the regulation of sex-specific RNA splicing, perhaps by acting as sites of interaction with trans-acting regulators. Furthermore, the data suggest that female-specific regulation of dsx RNA processing occurs by promoting the usage of the female splice acceptor site, rather than by repressing the usage of the alternative male-specific splice acceptor.

Amino Acid Sequence↗
PubMed1999

Mechanism of intrinsic transcription termination and antitermination.

Gene expression is modulated by regulatory elements that influence transcription elongation by RNA polymerase: terminators that disrupt the elongation complex and release RNA, and regulators that overcome termination signals. RNA release from Escherichia coli RNA polymerase can be induced by a complementary oligonucleotide that replaces the upstream half of the RNA hairpin stem of intrinsic terminator transcripts, implying that RNA hairpins act by extracting RNA from the transcription complex. A transcription antiterminator inhibits this activity of oligonucleotides and therefore protects the elongation complex from destabilizing attacks on the emerging transcript. These effects illuminate the structure of the complex and the mechanism of transcription termination.

Base Pairing↗
PubMed1989

Role of countertranscript RNA in the copy number control system of an IncB miniplasmid.

Transcriptional mapping studies of the IncB minireplicon pMU720 demonstrated the existence of a long RNA molecule, RNA II, whose 5' portion is complementary to the product of the incompatibility gene RNA I. By using gene fusion and transcriptional fusion plasmids, it was shown that RNA I regulated the expression of the RNA II gene product and that it did so primarily at the level of translation. The target of RNA I was mapped to lie within a 216-base region of RNA II containing the sequence complementary to RNA I. Introduction of the target for RNA I in trans increased the copy number of an IncB minireplicon, indicating that RNA I and RNA II form the basis of the copy number control system of IncB plasmids.

Amino Acid Sequence↗
PubMed1977

Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination.

Transcription termination at the attenuators of the trp operons of Escherichia coli and Salmonella typhimurium was studied in vitro using DNA restriction fragments as templates. Readthrough transcription beyond the terminators occurred with 5 and 30% efficiency, respectively, in E. coli and S. typhimurium. This difference is correlated with the stability of proposed secondary structures of the respective trp leader transcripts. Secondary structure analyses of the two leader transcripts revealed a well-conserved pattern of RNA base paring. This and the possibility that trp leader RNA is translated suggest a model for regulation of transcription termination that is based on ribosome movement along the RNA and a shift between alternative RNA base-pairing configuration.

Escherichia coli↗
PubMed2004

Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells.

Caveolin-1 is a scaffolding/regulatory protein that interacts with diverse signaling molecules in endothelial cells. To explore the role of this protein in receptor-modulated signaling pathways, we transfected bovine aortic endothelial cells (BAEC) with small interfering RNA (siRNA) duplexes to down-regulate caveolin-1 expression. Transfection of BAEC with duplex siRNA targeted against caveolin-1 mRNA selectively "knocked-down" the expression of caveolin-1 by approximately 90%, as demonstrated by immunoblot analyses of BAEC lysates. We used discontinuous sucrose gradients to purify caveolin-containing lipid rafts from siRNA-treated endothelial cells. Despite the near-total down-regulation of caveolin-1 expression, the lipid raft targeting of diverse signaling proteins (including the endothelial isoform of nitric-oxide synthase, Src-family tyrosine kinases, Galphaq and the insulin receptor) was unchanged. We explored the consequences of caveolin-1 knockdown on kinase pathways modulated by the agonists sphingosine-1 phosphate (S1P) and vascular endothelial growth factor (VEGF). siRNA-mediated caveolin-1 knockdown enhanced basal as well as S1P- and VEGF-induced phosphorylation of the protein kinase Akt and did not modify the basal or agonist-induced phosphorylation of extracellular signal-regulated kinases 1/2. Caveolin-1 knock-down also significantly enhanced the basal and agonist-induced activity of the small GTPase Rac. We used siRNA to down-regulate Rac expression in BAEC, and we observed that Rac knockdown significantly reduced basal, S1P-, and VEGF-induced Akt phosphorylation, suggesting a role for Rac activation in the caveolin siRNA-mediated increase in Akt phosphorylation. By using siRNA to knockdown caveolin-1 and Rac expression in cultured endothelial cells, we have found that caveolin-1 does not seem to be required for the targeting of signaling molecules to caveolae/lipid rafts and that caveolin-1 differentially modulates specific kinase pathways in endothelial cells.

Actins↗
PubMed1999

Subgenomic mRNA regulation by a distal RNA element in a (+)-strand RNA virus.

Subgenomic (sg) mRNAs are synthesized by (+)-strand RNA viruses to allow for efficient translation of products encoded 3' in their genomes. This strategy also provides a means for regulating the expression of such products via modulation of sg mRNA accumulation. We have studied the mechanism by which sg mRNAs levels are controlled in tomato bushy stunt virus, a small (+)-strand RNA virus which synthesizes two sg mRNAs during infections. Neither the viral capsid nor movement proteins were found to play any significant role in modulating the accumulation levels of either sg mRNA. Deletion analysis did, however, identify a 12-nt-long RNA sequence located approximately 1,000 nt upstream from the site of initiation of sg mRNA2 synthesis that was required specifically for accumulation of sg mRNA2. Further analysis revealed a potential base-pairing interaction between this sequence and a sequence located just 5' to the site of initiation for sg mRNA2 synthesis. Mutant genomes in which this interaction was either disrupted or maintained were analyzed and the results indicated a positive correlation between the predicted stability of the base-pairing interaction and the efficiency of sg mRNA2 accumulation. The functional significance of the long-distance interaction was further supported by phylogenetic sequence analysis which revealed conservation of base-pairing interactions of similar stability and relative position in the genomes of different tombusviruses. It is proposed that the upstream sequence represents a cis-acting RNA element which facilitates sg mRNA accumulation by promoting efficient synthesis of sg mRNA2 via a long-distance RNA-RNA interaction.

Amino Acid Sequence↗
PubMed2005

[Down-regulation of CT120A by RNA interference suppresses lung cancer cells growth].

OBJECTIVE: To validate our obtained outcomes and clarify the relationship between CT120A, a novel human plasma membrane-associated gene, and proliferation of lung cancer cells. METHODS: A vector-based small hairpin RNA (shRNA) was transfected into the human lung adenocarcinoma SPC-A-1 cells to specifically target CT120A cDNA. RT-PCR and Western blotting were used to analyze the CT120A expression. The cell proliferation rate was analyzed by BrdU-TdR incorporation assay, the ability of cells to grow in soft agarose and the tumorigenicity in nude mice were measured. Flow cytometry was performed to analyze cell apoptosis. RESULTS: When compared with the scrambled control cell line, CT120A transcripts were reduced by 70% and 50% in two shRNA-H stable transfectants, H2 and H3 clones, respectively. The protein of CT120A was reduced by about 80% in both the H2 and H3 clones. By BrdU incorporation assay, up to the 6th day a dramatic decrease in the cell growth rate (30% to 40%) was observed in the shRNA-H2 and shRNA-H3 cell lines. The colony formation rate in soft agarose of the two cell lines was about one half that of the control cells. In addition, a remarkable reduction of tumorigenicity of the two cell lines was observed as compared with that of the control. The suppression of CT120A expression also sensitized cells to ultraviolet-induced apoptosis. CONCLUSION: Down-regulation of CT120A by RNA interference suppresses lung cancer cell growth. The successful knockdown of CT120A expression by RNA interference implicates that CT120A may be a new candidate of drug target for treatment of lung cancers.

Adenocarcinoma↗
PubMed1997

Regulation of eukaryotic messenger RNA turnover.

We have demonstrated the existence of multiple mRNA binding proteins that interact specifically with defined regions in posttranscriptionally regulated mRNAs. These domains appear to be destabilizers whose function can be attenuated by the interaction with the specific binding proteins. Thus, the ability to alter mRNA decay rates on demand, given different environmental or intracellular conditions, appears to be mediated by controlling the localization, activity, and overall function of the cognate binding protein. Based on our limited experience, we predict that most, if not all, of similarly regulated mRNAs will ultimately be found to interact with regulatory mRNA binding proteins. Under conditions whereby the mRNA binding proteins are constitutively active (e.g., tumor cell lines), abnormal mRNA decay will result, with accumulation and overtranslation. Such appears to be the case for cytokines and possibly amyloid protein precursor mRNAs in cancer and Alzheimer's disease, respectively. Conversely, mutagenesis of these critical 3' untranslated region elements will likely have comparable deleterious effects on the regulation of gene expression. To the extent that such derangements exist in human disease, attention to understanding the mechanistic detail at this level may provide insights into the development of appropriate therapeutics or treatment strategies.

Amyloid beta-Protein Precursor↗
PubMed1983

Regulation of human ribosomal RNA transcription.

We have used a cell-free polymerase I transcription system derived from HeLa cells to study the regulation of human rRNA synthesis. Analysis of deletion mutants spanning the start site of transcription at nucleotide +1 indicates that the control region affecting initiation of human rRNA synthesis is contained within sequences from nucleotides -158 to +18. This promoter region can be subdivided into (i) a central segment of approximately 40 base pair that is required for transcription and (ii) flanking sequences that influence the efficiency of transcription in vitro. We have examined the in vitro transcriptional activity of the human extract under various conditions that are thought to modulate rRNA synthesis in vivo. Cell-free extracts prepared from HeLa cells infected with adenovirus 2 synthesize human rRNA at levels greatly decreased relative to uninfected cell extracts. By contrast, in vitro transcription of human rRNA is stimulated 2- to 3-fold by the addition of purified simian virus 40 large tumor antigen to the transcription reaction. Moreover, a mutant tumor antigen known to be defective for rRNA activation in vivo is incapable of stimulating rRNA synthesis in vitro. The ability to detect these different regulatory phenomena in vitro provides us with an experimental basis for investigating the molecular mechanisms that control rRNA synthesis.

Cell Transformation, Neoplastic↗
PubMed1991

Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: interactions between glucocorticoids and second messengers.

The role of glucocorticoids and second messenger systems in the regulation of the vasopressin (VP) gene was studied in the human small cell lung carcinoma cell line GLC-8. Small cell lung carcinoma GLC-8 cells express VP mRNA and contain both glucocorticoid and mineralocorticoid receptors. Treatment with the synthetic glucocorticoid dexamethasone when added alone at 10(-8) M had no effect on the VP mRNA level and decreased the level by 30% at 10(-6) M. However, the effect of dexamethasone changed to positive when cells were simultaneously treated with cAMP-enhancing agents. VP mRNA levels, which were elevated by 1.5- to 2-fold by the cAMP-enhancing agents alone, increased a further 1.5- to 3-fold by dexamethasone. Thus, the combined effect of dexamethasone and cAMP stimulation was a 3- to 7.5-fold increase in VP mRNA levels. Long term treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reduced the VP mRNA level by 75%. The TPA-suppressed VP mRNA levels could be up-regulated about 6-fold by simultaneous treatment with 8-bromo-cAMP. Dexamethasone did not alter the TPA-suppressed VP mRNA levels. These results indicate that both cAMP and protein kinase-C pathways as well as glucocorticoid receptors are involved in the regulation of VP mRNA levels and that these factors interact. This leads to a negative or positive response of VP gene expression to glucocorticoids in a state-dependent manner. The interactions may be of significance in a physiological context and relate to the different regulation of VP-expressing systems in the brain.

1-Methyl-3-isobutylxanthine↗
PubMed2007

Nuclear repositioning of the VSG promoter during developmental silencing in Trypanosoma brucei.

Interphase nuclear repositioning of chromosomes has been implicated in the epigenetic regulation of RNA polymerase (pol) II transcription. However, little is known about the nuclear position-dependent regulation of RNA pol I-transcribed loci. Trypanosoma brucei is an excellent model system to address this question because its two main surface protein genes, procyclin and variant surface glycoprotein (VSG), are transcribed by pol I and undergo distinct transcriptional activation or downregulation events during developmental differentiation. Although the monoallelically expressed VSG locus is exclusively localized to an extranucleolar body in the bloodstream form, in this study, we report that nonmutually exclusive procyclin genes are located at the nucleolar periphery. Interestingly, ribosomal DNA loci and pol I transcription activity are restricted to similar perinucleolar positions. Upon developmental transcriptional downregulation, however, the active VSG promoter selectively undergoes a rapid and dramatic repositioning to the nuclear envelope. Subsequently, the VSG promoter region was subjected to chromatin condensation. We propose a model whereby the VSG expression site pol I promoter is selectively targeted by temporal nuclear repositioning during developmental silencing.

Amanitins↗