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Results for “Translational repression”

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PubMed2005

[Micro-RNA and oncogenesis].

MicroRNA are endogenous molecules which negatively regulate the expression of a variety of genes. These tiny non coding RNA molecules--18 to 25 nucleotides in length--repress, with efficiency and specificity- translation of target mRNA into protein, according to a process akin to RNA interference. MiRNA are critical in the development of plants and mammals since they play a key role on proteins which regulate the strict spatiotemporal control of each tissue. Very recent reports published during 2005 summer show miRNA as also involved in oncogenesis. Specific miRNA elicit oncogenic and antiapoptotic properties in lymphoma models and glioblastoma, respectively. The expression profile of the two hundred miARN, so far identified, reflects the tumor tissue lineage, leading to a potential tool for diagnosis. The occurrence of miRNA in solid tumors and haematological neoplasia opens new avenues for understanding of oncogenesis and, likely, for management of cancer diseases.

Apoptosis↗

PubMedDate not supplied

[The difficult path of critical psychosomatic medicine].

In our present-day society that openly worships strength and secretly represses death, psychosomatic medicine is on the horns of a dilemma: either to externalize this repressive attitude and thus to translate it into reality so to say by de-interiorization, or to critically defend a mental health concept that can be considered as representing a unification of inner and outer ecology.

Forecasting↗

PubMed1990

Glucocorticoids repress ribosome biosynthesis in lymphosarcoma cells by affecting gene expression at the level of transcription, posttranscription and translation.

Growth arrest of P1798 murine lymphosarcoma cells by glucocorticoids is accompanied by a remarkable decrease in transcription of rRNA and translation of mRNAs encoding basic ribosomal proteins (rps). Here we report that the expression of other genes involved in ribosome biogenesis is repressed in dexamethasone-treated P1798 cells. These include posttranscriptionally regulated decline in the abundance of the mRNA and primary transcript of nucleolin; abrupt drop in the transcription rate of U3 small nucleolar RNA; and inhibition of translation of mRNAs coding for P2 and L5, acidic and basic rps, respectively. Normal expression of these genes is resumed upon hormonal withdrawal.

Animals↗

PubMed1997

Regulated unmasking of in vivo synthesized maternal mRNA at oocyte maturation. A role for the chaperone nucleoplasmin.

We examine the translational regulation of histone H4 mRNA when Xenopus laevis oocytes are induced to mature with progesterone. Histone H4 mRNA synthesized from plasmid templates microinjected into oocyte nuclei is translationally silenced (masked). This masked mRNA becomes translationally active only after oocyte maturation. In contrast, histone H4 mRNA injected into the oocyte cytoplasm is translationally active both before and after oocyte maturation. Thus, transcription in vivo is required to mask histone H4 mRNA and to allow subsequent translational regulation. Protein association with histone H4 mRNA synthesized in vivo was determined before and after oocyte maturation. UV cross-linking of radiolabeled RNA to protein and immunoprecipitation of cross-linked proteins reveals an increased association of the chaperone nucleoplasmin with ribonucleoprotein particles dependent on the oocyte maturation process. The Y-box protein FRGY2 inhibits translation of histone H4 mRNA in vitro. Nucleoplasmin is able to partially relieve this repression. We discuss the potential role of nuleoplasmin in the remodeling of repressive ribonucleoprotein particles containing maternal mRNA to facilitate translational activation.

Amino Acid Sequence↗

PubMed2007

The miRNA156/157 recognition element in the 3' UTR of the Arabidopsis SBP box gene SPL3 prevents early flowering by translational inhibition in seedlings.

miRNAs are a class of versatile small RNAs that control gene expression post-transcriptionally, governing many facets of plant cell functions. They interact with their target mRNA at a site of sequence complementarity and modulate their expression levels. Here, we provide evidence, based on transient assays and stable transgenic lines, that the 3' UTR of the Arabidopsis SBP box gene SPL3 contains a functional miRNA-responsive element (MRE) that is complementary to miR156 and miRNA157. Seedlings of transgenic lines constitutively over-expressing an SPL3 transgene either carrying an unaltered or a disrupted MRE accumulate considerable levels of SPL3 transcripts. However, while the unaltered MRE UTR does not allow the expression of detectable levels of SPL3 protein, the altered MRE does. Translational inhibition thus provides an important mechanism for miRNA-mediated post-transcriptional repression of SPL3. As a consequence of precocious translation of the constitutively expressed SPL3 transgene, due to the absence of a functional MRE, plants exhibit very early flowering in addition to frequent morphological changes.

Arabidopsis↗

PubMed1991

The nadI region of Salmonella typhimurium encodes a bifunctional regulatory protein.

Mutants of the nadI and pnuA genes were independently isolated on the basis of defects in repression of NAD biosynthetic genes and defects in transport nicotinamide mononucleotide (NMN). The mutations map at min 99 on the Salmonella chromosome, and the affected regions appear to be cotranscribed. Some pairs of nadI and pnuA mutations complement, suggesting the existence of independent functions. However, cis/trans tests with particular mutations provide evidence that both repressor and transport functions are actually performed by a single bifunctional protein. (This result confirms sequencing data of Foster and coworkers [J. W. Foster, Y. K. Park, T. Fenger, and M. P. Spector, J. Bacteriol. 172:4187-4196, 1990]). We have designated the gene for this bifunctional protein nadI and distinguish the regulatory and transport defects with phenotypic designations (R and T). When a nadI(R- T+) mutation (eliminating only repression function) is placed cis to a superrepressor mutation, nadI(Rs T-), the superrepression phenotype is lost. In contrast, placement of R- and Rs T- mutations in trans allows full superrepression. This result suggests that the transport function (eliminated by the Rs T- mutation) and the repression function are provided by the same protein. Insertion mutations in the promoter-proximal repressor region of the nadI gene eliminate transport function unless the inserted element can provide both for both transcription and translation start signals; this finding suggests that there is no transcriptional or translational start between the regions encoding repression and transport functions.

Bacterial Proteins↗

PubMed1998

Dihydroaeruginoic acid synthetase and pyochelin synthetase, products of the pchEF genes, are induced by extracellular pyochelin in Pseudomonas aeruginosa.

The siderophore pyochelin of Pseudomonas aeruginosa is derived from one molecule of salicylate and two molecules of cysteine. Two cotranscribed genes, pchEF, encoding peptide synthetases have been identified and characterized. pchE was required for the conversion of salicylate to dihydroaeruginoate (Dha), the condensation product of salicylate and one cysteine residue and pchF was essential for the synthesis of pyochelin from Dha. The deduced PchE (156 kDa) and PchF (197 kDa) proteins had adenylation, thiolation and condensation/cyclization motifs arranged as modules which are typical of those peptide synthetases forming thiazoline rings. The pchEF genes were coregulated with the pchDCBA operon, which provides enzymes for the synthesis (PchBA) and activation (PchD) of salicylate as well as a putative thioesterase (PchC). Expression of a translational pchE'-'lacZ fusion was strictly dependent on the PchR regulator and was induced by extracellular pyochelin, the end product of the pathway. Iron replete conditions led to Fur (ferric uptake regulator)-dependent repression of the pchE'-'lacZ fusion. A translational pchD'-'lacZ fusion was also positively regulated by PchR and pyochelin and repressed by Fur and iron. Thus, autoinduction by pyochelin (or ferric pyochelin) and repression by iron ensure a sensitive control of the pyochelin pathway in P. aeruginosa.

Amino Acid Sequence↗

PubMed1977

The effect of translation and transcription inhibitors on the synthesis of periplasmic phosphatases in E. coli.

Previous studies by others have indicated that the synthesis of secreted enzymes is unusually sensitive to many translation inhibitors and resistant, for about 30 min, to rifampicin. We have studied the sensitivity of secreted (periplasmic) phosphatases to such inhibitors. Alkaline phosphatase synthesis is more sensitive than total protein synthesis to tetracyclin and spectinomycin, but not to sparsomycin, streptomycin, chloramphenicol, kasugamycin, blasticidin S or thiostrepton; it is slightly more resistant than total protein synthesis to the latter two antibiotics. Acid hexose-phosphatase was also preferentially sensitive to tetracyclin and spectinomycin and also to kasugamycin. beta-galactosidase was also included in the study, as an intracellular enzyme, and was found to be preferentially inhibited ("repressed"), sometimes transiently, by all eight translation inhibitors. This effect did not seem to be mediated through cyclic AMP or guanosine tetraphosphate; the "repression" was still evident in mutants with altered rho factor indicating that it may also not be related to artificial polarity. Synthesis of both periplasmic phosphatases was immediately inhibited by rifampicin. These results differ from those found in previous studies with other organisms and suggest a reappraisal of the usual interpretation of these phenomena.

Acid Phosphatase↗

PubMed1986

Molecular events associated with glucose repression of invertase in Saccharomyces cerevisiae.

When S. cerevisiae growing in the presence of glucose (repressive condition) was shifted to higher temperatures, invertase was secreted. This secretion required protein synthesis, but was independent of RNA formation (Mormeneo & Sentandreu 1982). In addition accumulation of invertasespecific messenger RNA occurred in the absence of protein synthesis but was expressed only after synthesis of protein. Invertase mRNA was continuously synthesized under repressive conditions and the levels of this mRNA were regulated by the presence of glucose. The hexose regulated the concentration of this mRNA at the level of transcription and/or by sensitization of this messenger RNA. The expression of the invertase mRNA present in the cells under repressive conditions was also regulated by glucose at the level of translation and/or secretion. As a result of these processes, under repressive conditions invertase is eliminated before secretion takes place.

Culture Media↗

PubMed1990

TPA induces repression of EGF receptor gene expression.

Epidermal growth factor receptor gene expression in response to the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was analyzed in the A549 human lung adenocarcinoma cell line using DNA transfection. After 8 h of treatment a definite repression (45%) of EGF receptor gene transcription could be seen. Repression was maintained for up to 24 h. Little or no induction of transcription could be seen prior to the onset of repression for potential enhancer regions both upstream and downstream of the translation start site. The cis-element(s) responsible for repression were localized between residues -384 and -151 of the EGF receptor gene promoter region using a deletion plasmid series.

Cell Line↗

PubMed2005

DNA damage promotes histone deacetylase 4 nuclear localization and repression of G2/M promoters, via p53 C-terminal lysines.

Repression of G(2)/M promoters after DNA damage is an active mechanism that requires the p53 tumor suppressor. We have recently found that histone deacetylase 4 (HDAC4) is recruited on NF-Y-dependent repressed promoters. In this report, we describe the relationship between p53 and HDAC4 recruitment following DNA damage using immunofluorescence, chromatin immunoprecipitation, and transfection experiments. HDAC4 shuttles from the cytoplasm into the nucleus, following DNA damage, independently of the activation of p53 and becomes associated with promoters through a p53-dependent mechanism. The C-terminal lysines of p53, which are acetylated and methylated, are required for HDAC4 recruitment and transcriptional repression. Trichostatin treatment, but not HDAC4 functional inactivation, relieves the adriamycin-mediated repression of G(2)/M promoters. Our results indicate that HDAC4 is a component of the DNA damage response and that post-translational modifications of p53 are important for repression of G(2)/M genes.

Animals↗

PubMed1997

Repression of retrovirus-mediated transgene expression by interferons: implications for gene therapy.

Retrovirus-mediated gene transfer is commonly used in gene therapy protocols and has the potential to provide long-term expression of the transgene. Although expression of a retrovirus-delivered transgene is satisfactory in cultured cells, it has been difficult to achieve consistent and high-level expression in vivo. In this investigation, we explored the possibility of modulating transgene expression by host-derived cytokines. Normal human keratinocytes and dermal fibroblasts were transduced with recombinant retroviruses expressing a reporter gene (lacZ). Treatment of transduced cells with a proinflammatory cytokine, gamma interferon (IFN-gamma), significantly reduced lacZ expression to less than 25% of that of nontreated cells. The inhibition was concentration dependent (peak at 5 ng/ml) and time dependent (maximal at 16 h for transcript and 24 h for protein); expression remained repressed in the continued presence of IFN-gamma but returned to normal levels 24 h after IFN-gamma withdrawal. The decrease in beta-galactosidase activity appeared to result from decrease in steady-state lacZ mRNA levels. Inhibitors of transcription and translation blocked IFN-gamma-induced repression, suggesting involvement of newly synthesized protein intermediates. Similar results were obtained by treatment of transduced cells with IFN-alpha but not with other proinflammatory cytokines, including tumor necrosis factor alpha, interleukin-2 (IL-1), IL-4, and granulocyte colony-stimulating factor. Although the level of lacZ mRNA was reduced by >70% following IFN treatment, the rate of lacZ transcription was not significantly different from that for nontreated cells. These results suggest that IFN-mediated regulation of transgene expression is at a posttranscriptional level. Interestingly, IFN-gamma also suppressed transgene expression driven by a cellular promoter (involucrin) inserted in an internal position in the retroviral vector. The presence of the overlapping 3' untranslated regions in transcripts initiated from the internal promoter and the long terminal repeat is suggestive of a posttranscriptional regulation, likely at the level of RNA stabilization. These results provide direct evidence for modulatory effects of IFNs on retrovirus-mediated transgene expression and suggest that gene therapy results may be altered by host inflammatory responses.

3T3 Cells↗

PubMed1987

Transcriptional and translational signals of the uidA gene in Escherichia coli K12.

The expression of uidA is negatively controlled by the products of the uidR and uxuR genes and is sensitive to catabolite repression. The locations of the transcriptional and translational signals of uidA were determined using lac gene fusions and S1 mapping experiments. The promoter structure of uidA resembles that of a promoter activated by cAMP receptor protein (CRP); putative control regions are located at positions -10 and -35 (relative to the transcription start site), are separated by more than 17 bp and exhibit poor homology with the normally recognized consensus sequences. Moreover, 80 bp separate the promoter from the translational signals. No CRP binding site was detected in the promoter region of uidA. Two operator sites, 01 and 02, were identified: 01 has a greater affinity for the UidR repressor, whereas 02 has a greater affinity for the UxuR repressor, but the two repressor molecules are able to bind at both the 01 and 02 sites. Analysis of two operator constitutive mutations allowed the location of one of the two UidR repressor binding sites; it contains palindromic units spanning the TaqI site of the uidA control region.

Base Sequence↗

PubMed2003

RNA localization and its role in the spatially restricted protein synthesis.

RNA localization is an evolutionarily conserved phenomenon that occurs in uni- and multi-cellular animal and plant species. Localized RNA plays a role in the establishment of cell polarity and/or the determination of cell fate. In recent years, it became evident that the major function of RNA localization is the creation of a high concentration of proteins in specific cellular compartments. The movement of RNA involves interactions between targeting signals within the RNA molecule, cytoskeleton, and molecular motors. Translocating RNA must be translationally silent, and on-site translation at the destination site requires a de-repression mechanism. This is probably achieved by sequestering RNA and the regulators of translation within the multiprotein RNP complexes that co-translocate all the components to the ultimate destination within the cell.

Animals↗

PubMed1997

A novel inhibitor of cap-dependent translation initiation in yeast: p20 competes with eIF4G for binding to eIF4E.

In the yeast Saccharomyces cerevisiae a small protein named p20 is found associated with translation initiation factor eIF4E, the mRNA cap-binding protein. We demonstrate here that p20 is a repressor of cap-dependent translation initiation. p20 shows amino acid sequence homology to a region of eIF4G, the large subunit of the cap-binding protein complex eIF4F, which carries the binding site for eIF4E. Both, eIF4G and p20 bind to eIF4E and compete with each other for binding to eIF4E. The eIF4E-p20 complex can bind to the cap structure and inhibit cap-dependent but not cap-independent translation initiation: the translation of a mRNA with the 67 nucleotide omega sequence of tobacco mosaic virus in its 5' untranslated region (which was previously shown to render translation cap-independent) is not inhibited by p20. Whereas the translation of the same mRNA lacking the omega sequence is strongly inhibited by p20. Disruption of CAF20, the gene encoding p20, stimulates the growth of yeast cells, overexpression of p20 causes slower growth of yeast cells. These results show that p20 is a regulator of eIF4E activity which represses cap-dependent initiation of translation by interfering with the interaction of eIF4E with eIF4G, e.g. the formation of the eIF4F-complex.

Amino Acid Sequence↗

PubMed2005

Beyond the Xi: macroH2A chromatin distribution and post-translational modification in an avian system.

MacroH2A (mH2A) is a histone variant that is enriched in the inactivated X-chromosomes of mammalian females. To characterize the role of this protein in other nuclear processes we isolated chromatin particles from chicken liver, a vertebrate system that does not undergo X-inactivation. Chromatin digestion and fractionation studies determined that mH2A is evenly distributed at several levels of chromatin structure and stabilizes the nucleosome core particle in solution. However, at the level of the chromatosome, selective salt precipitation showed the existence of a mutually exclusive relationship between mH2A and H1, which may reveal functional redundancy between these proteins. Two-dimensional gel electrophoresis demonstrated the presence of one major population of mH2A containing nucleosomes, which may become ADP-ribosylated. This report provides new clues into how mH2A distribution and a previously unidentified post-translational modification may help regulate the repression of autosomal chromatin.

Animals↗

PubMed1996

Uncoordinated regulation of histone H1(0)synthesis and H1(0) mRNA level.

H1(0) are H1 histone variants that accumulate in the chromatin of many differentiated tissues and may contribute to the modifications of transcriptional activities. Using B16 melanoma and Friend erythroleukemia cells, which can be induced to differentiate, I studied H1(0) mRNA translation regulation by measuring the H1(0) synthesis rate with radioactive labelling. It is first confirmed, in a new cellular model (B16 melanoma), that translation of H1(0) mRNAs is highly repressed during differentiation-induced accumulation of H1(0) protein. To show that this result was not merely reflecting an inefficiency in the translation of H1(0) mRNA, I used physiological and non-physiological methods to modulate H1(0) mRNA levels. Modifications of H1(0) mRNA levels appeared inefficient in changing the translation rate of H1(0) mRNAs. These results indicate that H1(0) mRNA levels may not always control the level of histone H1(0) synthesis which might be regulated independently from the mRNA level, probably in concert with the cellular stability of the protein.

Animals↗

PubMed1992

Selective translational control and nonspecific posttranscriptional regulation of ribosomal protein gene expression during development and regeneration of rat liver.

Mammalian liver development is accompanied by a transition from rapid growth in the fetus to a quiescent state in the adult. However, extensive proliferation can be induced in the adult liver by partial hepatectomy. In this study, we examined the regulation of ribosomal protein (rp) gene expression in the developing and regenerating rat liver. Our results indicate that the translation of rp mRNAs is selectively repressed by about 70% upon development from fetal to adult life, as illustrated by the decrease in ribosomal loading. In addition, the relative abundance of these mRNAs, like that of several other, but not all, housekeeping mRNAs, declines during development through a posttranscriptional mechanism. When liver cells commence growth following partial hepatectomy, translation of rp mRNAs is resumed to near-maximal capacity, as judged by their very efficient recruitment into polysomes. The concomitant increase in the abundance rp mRNAs under these circumstances is achieved by a posttranscriptional mechanism. The apparent fluctuations in the translation efficiency of rp mRNAs are accompanied by parallel changes in the expression of the genes encoding the initiation factors eIF-4E and eIF-4A. Our results indicate that selective translational control of rp mRNAs in mammals is not confined to manipulated cells in culture but constitutes an important regulatory mechanism operating in vivo in the course of liver development and regeneration.

Animals↗