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Results for “Translational repression”

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PubMed1976

Translational, autogenous regulation of gene 32 expression during bacteriophage T4 infection.

Functional half-life measurements of the bacteriophage T4 gene 32 messenger RNA indicate that this mRNA is extremely stable. Regulation of gene 32 expression at the transcriptional level cannot account for the rapidity with which P32 synthesis can be repressed. Furthermore, derepression of P32 synthesis occurs in the presence of rifampicin, a drug which inhibits transcriptional initiation. In addition, T4-infected cultures in which P32 expression is repressed possess almost as much gene 32 mRNA as derepressed cultures. We conclude that expression of the T4 gene 32 protein is regulated at the level of translation.

Coliphages↗

PubMed1989

Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition.

The GCD2 gene product is required in conditions of amino acid sufficiency to repress the synthesis of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCD2 is also required unconditionally for cell viability. The constitutive derepression of GCN4 expression and temperature sensitivity for growth associated with GCD2 alleles, known as gcd12 mutations, are completely masked by wild-type GCN3, a positive regulator of GCN4 expression. This observation suggests that GCN3 can promote or at least partially substitute for GCD2 function in normal growth conditions, while acting as an antagonist of GCD2 in amino acid starvation conditions. We report here that the predicted amino acid sequence of GCN3 shows extensive similarity with the carboxyl-terminal portion of GCD2. Based on this finding, it seems likely that gcd12 mutations specifically affect the domain of GCD2 that is similar in sequence to GCN3. We propose that GCN3 can substitute for this domain in a gcd12 mutant grown in normal growth conditions, and that modification of GCN3 in starvation conditions causes it to interfere with, rather than substitute for GCD2 function. A gcd2 deletion and gcd2-1 are each expected to inactivate a second domain for which GCN3 cannot substitute, accounting for the inability of GCN3 to mask the phenotypes associated with these mutations.

Amino Acid Sequence↗

PubMed2000

FlbT, the post-transcriptional regulator of flagellin synthesis in Caulobacter crescentus, interacts with the 5' untranslated region of flagellin mRNA.

Flagellar gene expression' in Caulobacter crescentus is regulated by a complex trans-acting hierarchy, in which the assembly of early structural proteins is required for the expression of later structural proteins. The flagellins that comprise the filament are regulated at both the transcriptional and the post-transcriptional levels. Post-transcriptional regulation is sensitive to the assembly of the flagellar basal body and hook structures. In mutant strains lacking these structures, flagellin genes are transcribed, but not translated. Mutations in the flagellar regulatory gene, flbT, restore flagellin translation in the absence of flagellar assembly. In this report, we investigate the mechanism of FlbT-mediated post-transcriptional regulation. We show that FlbT is associated with the 5' untranslated region (UTR) of fljK (25 kDa flagellin) mRNA and that this association requires a predicted loop structure in the transcript. Mutations within this loop abolished FlbT association and resulted in increased mRNA stability, indicating that FlbT promotes the degradation of flagellin mRNA by associating with the 5' UTR. We also assayed the effects on gene expression using mutant transcripts fused to lacZ. Interestingly, the mutant transcript that failed to associate with FlbT in vitro was still repressed in mutants defective in flagellum assembly, suggesting that other factors in addition to FlbT couple assembly to translation.

5' Untranslated Regions↗

PubMed1980

[Localization of secreted enzyme-induced repression of its synthesis by the cells].

It was shown that under conditions of regulation of secreted enzyme synthesis by its concentration in microorganisms, the repression of synthesis of the enzyme protein polypeptide chain and the concomitant partial repression of labelled amino acid transport into the cells occur. The regulatory effect can be exerted in the absence of transcription as well. These effects are not realized at the post-transcription or post-translation levels.

Amino Acids↗

PubMed2000

Glucose depletion rapidly inhibits translation initiation in yeast.

Glucose performs key functions as a signaling molecule in the yeast Saccharomyces cerevisiae. Glucose depletion is known to regulate gene expression via pathways that lead to derepression of genes at the transcriptional level. In this study, we have investigated the effect of glucose depletion on protein synthesis. We discovered that glucose withdrawal from the growth medium led to a rapid inhibition of protein synthesis and that this effect was readily reversed upon readdition of glucose. Neither the inhibition nor the reactivation of translation required new transcription. This inhibition also did not require activation of the amino acid starvation pathway or inactivation of the TOR kinase pathway. However, mutants in the glucose repression (reg1, glc7, hxk2, and ssn6), hexose transporter induction (snf3 rgt2), and cAMP-dependent protein kinase (tpk1(w) and tpk2(w)) pathways were resistant to the inhibitory effects of glucose withdrawal on translation. These findings highlight the intimate connection between the nutrient status of the cell and its translational capacity. They also help to define a new area of posttranscriptional regulation in yeast.

Adenosine Triphosphate↗

PubMed2001

Regulation of transcription of the Bacillus subtilis pyrG gene, encoding cytidine triphosphate synthetase.

The B. subtilis pyrG gene, which encodes CTP synthetase, is located far from the pyrimidine biosynthetic operon on the chromosome and is independently regulated. The pyrG promoter and 5' leader were fused to lacZ and integrated into the chromosomes of several B. subtilis strains having mutations in genes of pyrimidine biosynthesis and salvage. These mutations allowed the intracellular pools of cytidine and uridine nucleotides to be manipulated by the composition of the growth medium. These experiments indicated that pyrG expression is repressed by cytidine nucleotides but is largely independent of uridine nucleotides. The start of pyrG transcription was mapped by primer extension to a position 178 nucleotides upstream of the translation initiation codon. A factor-independent termination hairpin lying between the pyrG promoter and its coding region is essential for regulation of pyrG expression. Primer-extended transcripts were equally abundant in repressed and derepressed cells when the primer bound upstream of the terminator, but they were much less abundant in repressed cells when the primer bound downstream of the terminator. Furthermore, deletion of the terminator from pyrG-lacZ fusions integrated into the chromosome yielded elevated levels of expression that was not repressible by cytidine. We suggest that cytidine repression of pyrG expression is mediated by an antitermination mechanism in which antitermination by a putative trans-acting protein is reduced by elevated levels of cytidine nucleotides. Conservation of sequences and secondary structural elements in the pyrG 5' leaders of several other gram-positive bacteria indicates that their pyrG genes are regulated by a similar mechanism.

5' Untranslated Regions↗

PubMed1974

Translational control induced by bacteriophage T7.

Phage T7 discontinues host gene expression by translational and transcriptional control mechanisms. Translational control is exerted by the T7 translational-repressor. This protein inhibits the synthesis of beta-galactosidase (EC 3.2.1.23) in vivo and in vitro and the synthesis of the T3 enzyme S-adenosylmethioninehydrolase (EC 3.3.1.-). The translational-repressor does not interfere with T7-specific enzyme synthesis. The T7 translational-repressor purifies with the initiation factors. The repressor interacts with the initiation of translation of host enzymes. The translational-repressor gene is close to the promotor for RNA polymerase of Escherichia coli.

Chromosome Mapping↗

PubMed2006

Analysis of the proteome of Pseudomonas putida KT2440 grown on different sources of carbon and energy.

Using 2D electrophoresis the protein expression pattern during growth on carbon sources with different impact on carbon catabolite repression of phenol degradation was analysed in a derivative of Pseudomonas putida KT2440. The cytosolic protein pattern of cells growing on phenol or the non-repressive substrate pyruvate was almost identical, but showed significant differences to that of cells growing with the repressive substrates succinate or glucose. Proteins, which were mainly expressed in the presence of phenol or pyruvate, could be assigned to the functional groups of transport, detoxification, stress response, amino acid, energy, carbohydrate and nucleotide metabolism. The addition of succinate to cells growing with phenol ('shift-up') resulted in the inhibition of the synthesis of these proteins. Proteins with enhanced expression at growth with succinate or glucose were proteins for de novo synthesis of nucleotides, amino acids and enzymes of the TCA cycle. The synthesis of proteins, necessary for phenol catabolism was regulated in different manners following the addition of succinate. Whereas the synthesis of Phl-proteins (subunits of the phenolhydroxylase) only decreased slowly, was the translation of the Cat-proteins (catechol 1,2-dioxygenase, cis,cis-muconate cycloisomerase and muconolactone isomerase) repressed immediately and the synthesis of the Pca-proteins (beta-ketoadipate enolactone hydrolase, beta-ketoadipate succinyl-CoA transferase and beta-ketoadipyl CoA thiolase) remained unaffected.

Bacterial Proteins↗

PubMed2003

A key role for the mRNA leader structure in translational control of ribosomal protein S1 synthesis in gamma-proteobacteria.

The translation initiation region (TIR) of the Escherichia coli rpsA mRNA coding for ribosomal protein S1 is characterized by a remarkable efficiency in driving protein synthesis despite the absence of the canonical Shine-Dalgarno element, and by a strong and specific autogenous repression in the presence of free S1 in trans. The efficient and autoregulated E.coli rpsA TIR comprises not less than 90 nt upstream of the translation start and can be unambiguously folded into three irregular hairpins (HI, HII and HIII) separated by A/U-rich single-stranded regions (ss1 and ss2). Phylogenetic comparison revealed that this specific fold is highly conserved in the gamma-subdivision of proteobacteria (but not in other subdivisions), except for the Pseudomonas group. To test phylogenetic predictions experimentally, we have generated rpsA'-'lacZ translational fusions by inserting the rpsA TIRs from various gamma-proteobacteria in-frame with the E.coli chromosomal lacZ gene. Measurements of their translation efficiency and negative regulation by excess protein S1 in trans have shown that only those rpsA TIRs which share the structural features with that of E.coli can govern efficient and regulated translation. We conclude that the E.coli-like mechanism for controlling the efficiency of protein S1 synthesis evolved after divergence of Pseudomona.

5' Untranslated Regions↗

PubMed1991

Regulation of the heat shock response in E coli: involvement of positive and negative cis-acting elements in translation control of sigma 32 synthesis.

When cells of E coli are transferred from 30 to 42 degrees C, the cellular level of sigma 32 (rpoH gene product) increases transiently, resulting in increased transcription of a set of heat shock genes. Both increased synthesis and increased stability of sigma 32 contribute to transient accumulation of sigma 32. Evidence suggests that synthesis of sigma 32 is enhanced primarily at the level of rpoH translation. We have constructed and examined the expression of deletion derivatives of rpoH-lacZ gene fusion at 30 degrees C and after shift to 42 degrees C. It was revealed that two cis-acting sequences within the rpoH coding region are involved in thermal regulation of fusion protein synthesis. One region immediately downstream of the initiation codon is required for high level expression, whereas the other internal region is involved in repression at low temperature. Thus, these regions act as positive and negative cis-elements in thermal regulation of rpoH translation. The rpoH mRNA secondary structure model suggesting an interplay between the two regions has been proposed to account for the temperature-induced sigma 32 synthesis as a primary cellular response to the heat shock stress.

Base Sequence↗

PubMed2002

A study of mesoderm patterning through the analysis of the regulation of Xmyf-5 expression.

Xenopus laevis has been a particularly useful model organism for identifying factors involved in the induction and patterning of the mesoderm, however, much remains to be learned about how these factors interact. The myogenic transcription factor Xmyf-5 is the earliest known gene to be expressed specifically in the dorsolateral mesoderm of the gastrula, a domain that is established by the interaction of dorsal and ventral signals. For this reason, we have begun to investigate how the expression of Xmyf-5 is regulated. We have identified a 7.28 kb Xenopus tropicalis Xmyf-5 (Xtmyf-5) genomic DNA fragment that accurately recapitulates the expression of the endogenous gene. Deletion and mutational analysis has identified HBX2, an essential element, approximately 1.2 kb upstream from the start of transcription, which is necessary for both activation and repression of Xtmyf-5 expression, implying that positional information is integrated at this site. Electrophoretic mobility shift assays demonstrate that HBX2 specifically interacts with gastrula stage embryonic extracts and that in vitro translated Xvent-1 protein binds to one of its functional motifs. Combined with gain- and loss-of-function experiments, the promoter analysis described here suggests that Xvent-1 functions to repress Xmyf-5 expression in the ventral domain of the marginal zone. Furthermore, the identification of HBX2 provides a tool with which to identify other molecules involved in the regulation of Xmyf-5 expression during gastrulation.

Amino Acid Motifs↗

PubMed2006

Global effects of homocysteine on transcription in Escherichia coli: induction of the gene for the major cold-shock protein, CspA.

Homocysteine (Hcy) is a thiol-containing amino acid that is considered to be medically important because it is linked to the development of several life-threatening diseases in humans, including cardiovascular disease and stroke. It inhibits the growth of Escherichia coli when supplied in the growth medium. Growth inhibition is believed to arise as a result of partial starvation for isoleucine, which occurs because Hcy perturbs the biosynthesis of this amino acid. This study attempted to further elucidate the inhibitory mode of action of Hcy by examining the impact of exogenously supplied Hcy on the transcriptome. Using gene macroarrays the transcript levels corresponding to 68 genes were found to be reproducibly altered in the presence of 0.5 mM Hcy. Of these genes, the biggest functional groups affected were those involved in translation (25 genes) and in amino acid metabolism (19 genes). Genes involved in protection against oxidative stress were repressed in Hcy-treated cells and this correlated with a decrease in catalase activity. The gene showing the strongest induction by Hcy was cspA, which encodes the major cold-shock protein CspA. RT-PCR and reporter fusion experiments confirmed that cspA was induced by Hcy. Induction of cspA by Hcy was not caused by nutritional upshift, a stimulus known to induce CspA expression, nor was it dependent on the presence of a functional CspA protein. The induction of cspA by Hcy was suppressed when isoleucine was included in the growth medium. These data suggest that the induction of CspA expression in the presence of Hcy occurs because of a limitation for isoleucine. The possibility that Hcy-induced cspA expression is triggered by translational stalling that occurs when the cells are limited for isoleucine is discussed.

Amino Acids↗

PubMed2004

Cyclic adenosine 5'-monophosphate response element modulator is responsible for the decreased expression of c-fos and activator protein-1 binding in T cells from patients with systemic lupus erythematosus.

T cells from patients with systemic lupus erythematosus express increased levels of the cAMP response element modulator (CREM) that has been shown to bind to the IL-2 promoter and suppress its activity. In this study, we demonstrate that CREM binds to the proximal promoter of the c-fos proto-oncogene in live systemic lupus erythematosus T cells and represses its expression following stimulation in vitro. Decreased levels of c-fos protein result in decreased AP-1 activity, as determined in shift assays. Blockade of the translation of CREM mRNA with an antisense CREM vector increases the expression of c-fos and the AP-1 activity. The levels of c-fos mRNA vary with disease activity. We conclude that CREM represses the expression of c-fos and limits the activity of the enhancer AP-1. Thus, CREM is involved indirectly in the modulation of transcriptional regulation of multiple genes including IL-2.

Adult↗

PubMed1997

Transcriptional and translational control of the genes for the mating pair formation apparatus of promiscuous IncP plasmids.

The trb operon of broad-host-range plasmid RK2 encodes most of the genes required for formation of mating-pair apparatus and is thus essential for the promiscuous spread of this plasmid. Only two promoters, lying upstream of trbA and trbB, have been identified for this operon. trbB encodes a protein belonging to a large family of proteins which function in the assembly of apparatuses associated with the cell surface. trbA encodes a repressor protein, one of whose targets is the trbB promoter. trbAp is arranged as a face-to-face divergent promoter with trfAp, the strongest of the three promoters in this region. trfAp completely inhibits trbAp unless it is repressed by the KorA protein, a key regulator encoded in the plasmid's central control operon. We show that when trfAp is firing constitutively, it also appears to interfere with trbBp, but that trbBp activity increases when trfAp activity is decreased by repression or mutation. A second global regulator encoded in the central control operon, KorB, represses trbBp, trfAp, and trbAp. The results presented here show that both KorB and TrbA are necessary for full repression of trbBp. The region between trbA and trbB encodes a large inverted repeat which has been proposed to modulate translation of trbB on transcripts which are initiated at trbAp but not trbBp. Using translational fusions to lacZ, we show that translation of trbB is completely blocked when transcripts incorporate the inverted repeat upstream of trbB but proceeds with reasonable efficiency when deletions remove the sequences predicted to sequester the ribosome binding site. Results from both transcriptional fusion and direct measurement of transcript size and intensity by Northern blot analysis show that most trbA transcripts are monocistronic and serve to express only trbA, although some transcription continues into trbB. The monocistronic trbA transcript appears to be the result of transcription termination downstream of trbA. Thus, trbAp and trbA appear to form an operon distinct from the trbB-trbP operon. Consequently, trbA and the switch that controls its expression help to provide the sequential steps which allow efficient expression of transfer genes during plasmid establishment but tight repression once the plasmid is established.

Bacterial Proteins↗

PubMedDate not supplied

Characterization of the adr1-1 nonsense mutation identifies the translational start of the yeast transcriptional activator ADR1.

We have characterized a nonsense mutation in the ADR1 gene that identifies the translational start of the ADR1 protein. The ADR1 gene of Saccharomyces cerevisiae is required for synthesis of the glucose-repressible alcohol dehydrogenase (ADH2). The adr1-1 mutation, which inhibits ADH2 expression, was identified as a C to G transversion at base pair +32. This alteration would result in a UGA nonsense codon in place of a serine codon that would lead to termination of the ADR1 polypeptide after the 10th amino acid. The effect of the adr1-1 mutation was partially reversed by UGA-tRNA suppressors, indicating that the adr1-1 mutation affects ADR1 expression at the translational level. These observations establish that the first available AUG in the ADR1 sequence is used as the translational start site of ADR1. Tyrosine or leucine UGA-tRNA-suppressors resulted in levels of adr1-1 activity similar to that found for a serine UGA-tRNA-suppressor, suggesting that serine residue-11 is not essential to ADR1 function. Northern analyses showed that the 5.1 kb ADR1 mRNA was two- to three-fold more abundant when isolated from a strain carrying the ADR1 allele than from an isogenic strain containing the adr1-1 allele. These data confirm that the 5.1 kb mRNA is the ADR1 mRNA and suggest that inhibition of adr1-1 mRNA translation results in more rapid degradation of the adr1-1 mRNA.

Alcohol Dehydrogenase↗

PubMed1995

Synthesis of non-translating or translating specialized ribosomes causes feedback regulation of ribosomal RNA synthesis in Escherichia coli.

Specialized ribosomes carry a mutant anti-Shine-Dalgarno region that disrupts the complementary base pairing that stabilizes the translation initiation complex with E. coli mRNAs. It has been reported that production of specialized ribosomes does not cause the inhibition of chromosomal rRNA synthesis that follows production of wild-type ribosomes. We proposed that enabling translation on specialized ribosomes by providing mRNA with a complementary mutation in the Shine-Dalgarno region would restore feedback regulation and inhibit chromosomal rRNA synthesis. With both our system and the system studied previously, we saw feedback regulation regardless of whether the specialized ribosomes were translating. As reported previously, transcription from plasmid-borne promoters decreased as chromosomal rRNA synthesis was repressed, suggesting that the lambda PL and tac promoters may be sensitive to the effector(s) of feedback regulation.

Base Sequence↗

PubMed1993

Heat-shock-induced protein synthesis is responsible for the switch-off of hsp70 transcription in Tetrahymena.

We had previously described that new RNA synthesis is required for expression of the heat shock protein HSP70. Here, we find that the HSP70 mRNA decreases its levels under stress conditions, heat shock (HS) or arsenite (As), and that its levels start to decline at the same time as maximal HSPs synthesis (including HSP70) occurs. This suggests that regulation of the hsp70 gene is mainly exerted at the transcriptional level. Accumulation of the HSP70 mRNA in cells stressed in presence of cycloheximide (CHX), indicates that (a) protein(s) non-existent before stress, possibly HSP70 itself (which is shown here to be relatively stable), is involved in negatively regulating hsp70 expression. Since degradation of the HSP70 mRNA is also shown to occur in cells heat-shocked under CHX, as seen from decay of its levels upon addition of actinomycin D (AMD), the protein(s) must repress hsp70 expression at the transcriptional level. Other conditions that affect normal protein synthesis, namely the translation inhibitor puromycin and the arginine-analog canavanine (shown here to be stress inducers in Tetrahymena pyriformis), also cause a delay in transcription-arrest of the HSP70 mRNA. Under severe stress conditions of HS (36 degrees C) or As (350 microM), the levels of HSP70 mRNA are higher than under mild stress conditions, however, no significant difference is seen in the pattern of HSP70 mRNA decay.

Animals↗

PubMed2005

Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression.

Staphylococcus aureus RNAIII is one of the largest regulatory RNAs, which controls several virulence genes encoding exoproteins and cell-wall-associated proteins. One of the RNAIII effects is the repression of spa gene (coding for the surface protein A) expression. Here, we show that spa repression occurs not only at the transcriptional level but also by RNAIII-mediated inhibition of translation and degradation of the stable spa mRNA by the double-strand-specific endoribonuclease III (RNase III). The 3' end domain of RNAIII, partially complementary to the 5' part of spa mRNA, efficiently anneals to spa mRNA through an initial loop-loop interaction. Although this annealing is sufficient to inhibit in vitro the formation of the translation initiation complex, the coordinated action of RNase III is essential in vivo to degrade the mRNA and irreversibly arrest translation. Our results further suggest that RNase III is recruited for targeting the paired RNAs. These findings add further complexity to the expression of the S. aureus virulon.

Antigens, Bacterial↗