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At least 109 records · Page 6Linked to original sources
PubMed2006

Outer membrane protein genes and their small non-coding RNA regulator genes in Photorhabdus luminescens.

INTRODUCTION: Three major outer membrane protein genes of Escherichia coli, ompF, ompC, and ompA respond to stress factors. Transcripts from these genes are regulated by the small non-coding RNAs micF, micC, and micA, respectively. Here we examine Photorhabdus luminescens, an organism that has a different habitat from E. coli for outer membrane protein genes and their regulatory RNA genes. RESULTS: By bioinformatics analysis of conserved genetic loci, mRNA 5'UTR sequences, RNA secondary structure motifs, upstream promoter regions and protein sequence homologies, an ompF -like porin gene in P. luminescens as well as a duplication of this gene have been predicted. Gene loci for micF RNA, as well as OmpC protein and its associated regulatory micC RNA, were not found. Significantly, a sequence bearing the appropriate signatures of the E. coli micA RNA was located. The ompA homolog was previously annotated in P. luminescens. CONCLUSION: Presence of an ompF-like porin in P. luminescens is in keeping with the necessity to allow for passage of small molecules into the cell. The apparent lack of ompC, micC and micF suggests that these genes are not essential to P. luminescens and ompC and micF in particular may have been lost when the organism entered its defined life cycle and partially protected habitat. Control of porin gene expression by RNA may be more prevalent in free- living cells where survival is dependent on the ability to make rapid adjustments in response to environmental stress. Regulation of ompA by micA may have been retained due to a necessity for ompA control during one or both stages of the P. luminescens life cycle.

Journal Article↗
PubMed2005

Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells.

Vertebrate genomes each encode hundreds of micro-RNAs (miRNAs), yet for few of these miRNAs is there empirical evidence as to which mRNA(s) they regulate. Here we report the identification of human lin-28 mRNA as a regulatory target of human miR-125b and its homolog miR-125a. Studies of miR-125b function in mouse P19 embryonal carcinoma cells induced to develop into neurons suggest a role for this regulatory miRNA in mammalian neuronal differentiation, since its increased concentration in these cells contributes to lin-28 downregulation. Within the lin-28 3' untranslated region (UTR) are two conserved miRNA responsive elements (miREs) that mediate repression by miR-125b and miR-125a. Simultaneous deletion of both miREs renders the lin-28 3' UTR almost completely insensitive to these miRNAs, indicating that these two miREs are the principal elements in the lin-28 3' UTR that respond to miR-125. At the 3' end of each element is an adenosine residue that makes a significant contribution to function irrespective of its complementarity to the 5'-terminal nucleotide of miR-125. By contrast to most earlier reports of gene repression by other miRNAs that are imperfectly complementary to their targets, lin-28 downregulation by miR-125 involves reductions in both translational efficiency and mRNA abundance. The decrease in the mRNA concentration is achieved by a posttranscriptional mechanism that is independent of the inhibitory effect on translation.

3' Untranslated Regions↗
PubMed2000

The retinoblastoma tumor suppressor protein targets distinct general transcription factors to regulate RNA polymerase III gene expression.

The retinoblastoma protein (RB) represses RNA polymerase III transcription effectively both in vivo and in vitro. Here we demonstrate that the general transcription factors snRNA-activating protein complex (SNAP(c)) and TATA binding protein (TBP) are important for RB repression of human U6 snRNA gene transcription by RNA polymerase III. RB is associated with SNAP(c) as detected by both coimmunoprecipitation of endogenous RB with SNAP(c) and cofractionation of RB and SNAP(c) during chromatographic purification. RB also interacts with two SNAP(c) subunits, SNAP43 and SNAP50. TBP or a combination of TBP and SNAP(c) restores efficient U6 transcription from RB-treated extracts, indicating that TBP is also involved in RB regulation. In contrast, the TBP-containing complex TFIIIB restores adenovirus VAI but not human U6 transcription in RB-treated extracts, suggesting that TFIIIB is important for RB regulation of tRNA-like genes. These results suggest that different classes of RNA polymerase III-transcribed genes have distinct general transcription factor requirements for repression by RB.

Adenoviruses, Human↗
PubMed1998

Exon sequence is required for regulated RNA splicing of the human fibroblast growth factor receptor-1 alpha-exon.

Alternative RNA processing of the human fibroblast growth factor receptor-1 transcript results in receptor forms that vary in their affinity for fibroblast growth factor. An alternative RNA processing event involving recognition of the alpha-exon is deregulated during neoplastic transformation of glial cells. We have previously established a splicing reporter/transfection cell culture model system to identify sequences involved in recognition of this exon. In this study, the system was used to identify two sequence elements that differentially function to regulate splicing of this exon. Exclusion of the alpha-exon in glioblastoma cells specifically required the downstream intron sequence comprising the 5'-splice site. Replacement or mutation of this sequence increasing complementarity to U1 RNA resulted in enhanced exon recognition in SNB-19 glioblastoma cells. Sequences within the exon were found to be required for alpha-exon inclusion. Deletion and gain-of-function experiments identified a 69-nucleotide exon sequence that was specifically required for alpha-exon inclusion. These studies indicate that multiple sequences are required for the regulated recognition of the alpha-exon.

Alternative Splicing↗
PubMed2001

RNA-Regulated TRA-1 nuclear export controls sexual fate.

TRA-1, a member of the GLI family of transcription factors, is required for C. elegans female development. We find that TRA-1 has a sex-specific distribution consistent with its role in female development: nuclear TRA-1 is higher in hermaphrodite intestines and in specific germline regions than in males. TRA-1 patterns rely on nuclear export since treatment with leptomycin B, a CRM1-dependent export inhibitor, increases nuclearTRA-1 in males. TRA-1 export requires TRA-1 binding to the tra-2 3' untranslated region (3' UTR), as disruption of binding increases nuclear TRA-1 and female development. Our data are consistent with coexport of a TRA-1/tra-2 mRNA complex reducing TRA-1 nuclear activity, and identify an interesting RNA-based mechanism for controlling transcriptional activity and cell fate determination.

3' Untranslated Regions↗
PubMed1999

Transcriptional cofactor CA150 regulates RNA polymerase II elongation in a TATA-box-dependent manner.

Tat protein strongly activates transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by enhancing the elongation efficiency of RNA polymerase II complexes. Tat-mediated transcriptional activation requires cellular cofactors and specific cis-acting elements within the HIV-1 promoter, among them a functional TATA box. Here, we have investigated the mechanism by which one of these cofactors, termed CA150, regulates HIV-1 transcription in vivo. We present a series of functional assays that demonstrate that the regulation of the HIV-1 LTR by CA150 has the same functional requirements as the activation by Tat. We found that CA150 affects elongation of transcription complexes assembled on the HIV-1 promoter in a TATA-box-dependent manner. We discuss the data in terms of the involvement of CA150 in the regulation of Tat-activated HIV-1 gene expression. In addition, we also provide evidence suggesting a role for CA150 in the regulation of cellular transcriptional processes.

Cell Line, Transformed↗
PubMed2001

Double-stranded RNA regulates IL-4 expression.

dsRNA, as genomic fragment, replicative intermediate, or stem and loop structure in cells infected by viruses, can act to signal the immune system of the presence of viral infections. Although most viral infections are associated with strong Th1 immune responses, Th2-type responses have also been observed. In this study, we characterize the effects of dsRNA on the induction of Th2 responses in human lymphocytes. We report that in addition to the well-known Th1-inducing capabilities of dsRNA, treatment of human lymphocytes with low concentrations of dsRNA (0.1-1 microg/ml) leads to the expression of the prototypic Th2 cytokine IL-4. This induction was accompanied with the concentration-dependent activation of NF-kappaB and NF-AT2 but not NF-AT1. In addition, dsRNA can directly activate an IL-4 promoter-driven chloramphenicol acetyltransferase reporter gene in transiently transfected Jurkat cells. These results are the first demonstration of a non-TCR-associated activator of NF-AT in human cells and suggest that dsRNA directly influences IL-4 gene expression through its effect on NF-AT activation. Our data provide support for the idea that dsRNA at low concentrations in vivo may induce a Th2-dominant response that is not optimal for protective immunity to the virus.

DNA-Binding Proteins↗
PubMed2004

An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region.

The Kcnq1 imprinting control region (ICR) located in intron 10 of the Kcnq1 gene is unmethylated on the paternal chromosome and methylated on the maternal chromosome and has been implicated in the manifestation of parent-of-origin-specific expression of six neighboring genes. The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region. To elucidate whether the Kcnq1ot1 RNA plays a role in the bidirectional silencing activity of the Kcnq1 ICR, we have characterized factor binding sites by genomic footprinting and tested the functional consequence of various deletions of these binding sites in an episome-based system. Deletion of the elements necessary for Kcnq1ot1 promoter function resulted in the loss of silencing activity. Furthermore, interruption of Kcnq1ot1 RNA production by the insertion of a polyadenylation sequence downstream of the promoter also caused a loss of both silencing activity and methylation spreading. Thus, the antisense RNA plays a key role in the silencing function of the ICR. Double-stranded RNA (dsRNA)-mediated RNA interference is unlikely to be involved, as the ICR is active irrespective of the simultaneous production of dsRNA from the genes it silences.

Base Sequence↗
PubMed1995

Ecdysone Regulated RNA synthesis in Drosophila larval salivary glands.

The changes in total and ribosomal RNA (rRNA) synthesis in cultured larval salivary glands of Drosophila in response to steroid hormone ecdysone have been studied. By using the incorporation of [3H]-uridine or [32P]-UTP into salivary gland cells, followed by RNA extraction and electrophoretic or sucrose gradient fractionation it was found that physiological concentrations of ecdysone stimulate the synthesis of rRNA. Administration of selective transcription inhibitors (actinomycin D, alpha-amanitin, cordycepin, DRB, and 5- fluorouridine) as well as protein synthesis inhibitors (cycloheximide, puromycin) showed that early response to ecdysone involved a direct stimulation of rDNA transcription, probably by ecdysone-ecdysone receptor complex, and is independent of protein synthesis. In later stages of the response to ecdysone, as revealed again using transcription and protein synthesis inhibitors, the synthesis of rRNA is dependent on the factor(s) produced during early stages of the response, in the manner which is very similar to sequential gene activation in chromosomal puffs. Experiments with the withdrawal of ecdysone from culture medium in early stages of its action show similar negative effects on rRNA synthesis as inhibitors of RNA polymerase II, thus proving the existence of parallel mechanism controlling induction of specific chromosomal puffs and transcription of rDNA. The data presented suggest that, in addition to the expression of tissue and developmentally-specific genes, the regulation of rDNA transcription, along with the production of ribosomes, might be required for Drosophila metamorphosis. The results are discussed in the light of vertebrate's steroid hormone action on ribosomal genes.

Journal Article↗
PubMed1999

Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation.

Monoclonal antibodies that recognize specific carboxyl-terminal domain (CTD) phosphoepitopes were used to examine CTD phosphorylation in yeast cells lacking carboxyl-terminal domain kinase I (CTDK-I). We show that deletion of the kinase subunit CTK1 results in an increase in phosphorylation of serine in position 5 (Ser(5)) of the CTD repeat (Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7)) during logarithmic growth. This result indicates that CTDK-I negatively regulates CTD Ser(5) phosphorylation. We also show that CTK1 deletion (ctk1Delta) eliminates the transient increase in CTD serine 2 (Ser(2)) phosphorylation observed during the diauxic shift. This result suggests that CTDK-I may play a direct role in phosphorylating CTD Ser(2) in response to nutrient depletion. Northern blot analysis was used to show that genes normally induced during the diauxic shift are not properly induced in a ctk1Delta strain. Glycogen synthase (GSY2) and cytosolic catalase (CTT1) mRNA levels increase about 10-fold in wild-type cells, but this increase is not observed in ctk1Delta cells suggesting that increased message levels may require Ser(2) phosphorylation. Heat shock also induces Ser(2) phosphorylation, but we show here that this change in CTD modification and an accompanying induction of heat shock gene expression is independent of CTDK-I. The observation that SSA3/SSA4 expression is increased in ctk1Delta cells grown at normal temperature suggests a possible role for CTDK-I in transcription repression. We discuss several possible positive and negative roles for CTDK-I in regulating CTD phosphorylation and gene expression.

Catalase↗
PubMed1997

Effects of cholinergic denervation on seizure development and neurotrophin messenger RNA regulation in rapid hippocampal kindling.

Intraventricular 192 IgG-saporin was used to induce a selective lesion of basal forebrain cholinergic neurons in rats. When subjected to 40 rapid hippocampal kindling stimulations with 5-min intervals, these animals exhibited increased number of generalized seizures and a higher mean seizure grade in response to the first five stimulations, and required fewer stimuli to develop focal behavioural seizures, as compared to non-lesioned rats. In contrast, both groups showed similarly enhanced responsiveness when test stimulated four weeks later. Using in situ hybridization, cholinergic denervation was found to cause a significant decrease of basal brain-derived neurotrophic factor messenger RNA levels in the hippocampal formation and piriform cortex, whereas gene expression for nerve growth factor, neurotrophin-3, and TrkB and TrkC was unchanged. Four weeks after rapid kindling stimulations, basal levels of brain-derived neurotrophic factor messenger RNA in the dentate granule cells were restored to normal in the lesioned rats, whereas neurotrophin-3 messenger RNA levels were decreased. No differences in the seizure-evoked levels of neurotrophin and Trk messenger RNAs were detected, except in the dentate granule cell layer, which had significantly higher brain-derived neurotrophic factor messenger RNA expression in the lesioned animals at 2 h. In conclusion, the basal forebrain cholinergic system (i) dampens the severity of recurring seizures induced by rapid hippocampal kindling stimulations, but has no effect on the subsequent delayed phase of epileptogenesis; and (ii) exerts a tonic stimulation of basal brain-derived neurotrophic factor messenger RNA levels in the hippocampal formation and piriform cortex. The findings also indicate that the cholinergic lesion does not affect neurotrophin and Trk gene expression after recurring seizures, and that the kindling process leads to long-term changes in basal brain-derived neurotrophic factor and neurotrophin-3 messenger RNA levels in the denervated animals.

Acetylcholinesterase↗
PubMed2002

A noncoding RNA regulates human protease-activated receptor-1 gene during embryogenesis.

Activation of the human protease-activated receptor-1 (PAR-1) by thrombin leads to myriad functions essential for maintaining vascular integrity. Upregulation of PAR-1 expression is considered important in atherosclerosis, angiogenesis and tumor metastasis. In vitro analysis of the human PAR-1 promoter function revealed a positive regulatory element between -4.2 and -3.2 kb of the transcription start site. This element was examined in transgenic mice containing either 4.1 or 2.9 kb of the 5' flanking sequence driving a LacZ reporter gene. Only the 4.1 kb PAR-1 transgene was expressed in vivo and only during embryonic development. The transgene expression was observed only in developing arteries and not in veins. Further examination of this putative regulatory sequence identified a novel noncoding RNA (ncR-uPAR:noncoding RNA upstream of the PAR-1) gene at -3.4 kb. The ncR-uPAR upregulated PAR-1-core promoter-driven luciferase activity and mRNA expression in vitro in a Pol II-dependent manner. This noncoding RNA appears to act in trans, albeit locally at the adjacent PAR-1 promoter. These data suggest that an untranslated RNA plays a role in PAR-1 gene expression during embryonic growth.

Animals↗
PubMed2006

Introns regulate RNA and protein abundance in yeast.

The purpose of introns in the architecturally simple genome of Saccharomyces cerevisiae is not well understood. To assay the functional relevance of introns, a series of computational analyses and several detailed deletion studies were completed on the intronic genes of S. cerevisiae. Mining existing data from genomewide studies on yeast revealed that intron-containing genes produce more RNA and more protein and are more likely to be haplo-insufficient than nonintronic genes. These observations for all intronic genes held true for distinct subsets of genes including ribosomal, nonribosomal, duplicated, and nonduplicated. Corroborating the result of computational analyses, deletion of introns from three essential genes decreased cellular RNA levels and caused measurable growth defects. These data provide evidence that introns improve transcriptional and translational yield and are required for competitive growth of yeast.

Actins↗
PubMed2006

Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1.

Maf1 is an essential and specific mediator of transcriptional repression in the RNA polymerase (pol) III system. Maf1-dependent repression occurs in response to a wide range of conditions, suggesting that the protein itself is targeted by the major nutritional and stress-signaling pathways. We show that Maf1 is a substrate for cAMP-dependent PKA in vitro and is differentially phosphorylated on PKA sites in vivo under normal versus repressing conditions. PKA activity negatively regulates Maf1 function because strains with unregulated high PKA activity block repression of pol III transcription in vivo, and strains lacking all PKA activity are hyperrepressible. Nuclear accumulation of Maf1 is required for transcriptional repression and is regulated by two nuclear localization sequences in the protein. An analysis of PKA phosphosite mutants shows that the localization of Maf1 is affected via the N-terminal nuclear localization sequence. In particular, mutations that prevent phosphorylation at PKA consensus sites promote nuclear accumulation of Maf1 without inducing repression. These results indicate that negative regulation of Maf1 by PKA is achieved by inhibiting its nuclear import and suggest that a PKA-independent activation step is required for nuclear Maf1 to function in the repression of pol III transcription. Finally, we report a previously undescribed phenotype for Maf1 in tRNA gene-mediated silencing of nearby RNA pol II transcription.

Active Transport, Cell Nucleus↗
PubMed1996

Immunolesioning of basal forebrain cholinergic neurons facilitates hippocampal kindling and perturbs neurotrophin messenger RNA regulation.

The immunotoxin 192 IgG-saporin induces an efficient and specific lesion of low-affinity nerve growth factor receptor-bearing cholinergic neurons in the basal forebrain. Intraventricular injection of 192 IgG-saporin, which caused a complete loss of cholinergic afferents to the hippocampus and neocortex and a partial denervation of amygdala and piriform cortex, was found to markedly facilitate the initial stages of seizure development in hippocampal kindling. In contrast, the progression of kindling process from focal to generalized seizures was not affected. In situ hybridization demonstrated that basal levels of brain-derived neutrotrophic factor messenger RNA in the hippocampal formation and piriform cortex were significantly decreased by the lesion, which also attenuated the seizure-induced increase of brain-derived neurotrophic factor messenger RNA expression in the hippocampus and frontal cortex. In the dentate gyrus, the 192 IgG-saporin lesion selectively reduced the upregulation of messenger RNAs for brain-derived neurotrophic factor exons I and III after a generalized seizure, whereas the increase of exon II messenger RNA was unchanged. The lesion abolished the seizure-evoked increase of nerve growth factor and TrkC messenger RNA levels and decrease of neutrophin-3 messenger RNA expression in dentate granule cells, while TrkB messenger RNA levels were not affected. We conclude that the basal forebrain cholinergic system (1) suppresses kindling epileptogenesis in the hippocampus, and (2) enhances both basal and seizure-evoked brain-derived neurotrophic factor synthesis in the hippocampal formation and some cortical areas through a specific pattern of activation of promoters within the brain-derived neurotrophic factor gene.

Animals↗
PubMed1999

The redox state regulates RNA degradation in the chloroplast of Chlamydomonas reinhardtii.

A Chlamydomonas reinhardtii chloroplast transformant, designated MU7, carrying a chimeric (rbcL promoter: beta-glucuronidase [GUS]: psaB 3' end) gene whose transcripts have been found previously to be unstable in light (half-life of 20 min in light as opposed to a half-life of 5 h in the dark), was used to study the role of electron transport and of the redox state in the degradation of chloroplast transcripts in the light. Blocking photosynthetic electron transport with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) prevented the light-dependent breakdown of the pool of GUS transcripts in MU7 cells. Diamide, an oxidizing agent, caused a measurable delay in the degradation of GUS transcripts in the light. The addition of dithiothreitol (DTT), a dithiol reductant, to MU7 cells in which GUS transcript levels were stabilized by DCMU induced degradation of GUS transcripts. Similarly, DTT induced a decrease in the levels of GUS transcripts when added to MU7 cells in the dark period of the light/dark cycle, a period in which GUS transcript levels normally increase. The levels of transcripts of endogenous chloroplast genes were affected by DCMU and DTT in the same direction as levels of GUS transcripts. The results suggest a regulatory role of the redox state in the degradation of chloroplast transcripts in C. reinhardtii.

Animals↗