Translational control of antibody synthesis. Control of light chain production.
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “Translational control”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Translational control by the La antigen. Structure requirements for rescue of the double-stranded RNA-mediated inhibition of protein synthesis.
The La antigen is a protein which can bind both single-stranded and double-stranded forms of RNA and has regulatory effects on gene expression at the levels of transcription and translation. It was previously shown to inhibit the activation of the dsRNA-dependent protein kinase PKR by sequestering and/or unwinding double-stranded RNA. Here, we demonstrate that, as predicted by these properties, the La antigen can rescue protein synthesis in the reticulocyte lysate system from inhibition by low concentrations of dsRNA. This effect is reversed by higher concentrations of dsRNA. Using a series of deletion mutants we have investigated the structural features of the La antigen that are required for these effects. The ability to bind dsRNA is influenced by regions within both the previously characterized N-terminal RNP motif and the C-terminal half of the protein. La mutants with either N-terminal or C-terminal deletions retain the ability to inhibit the protein kinase activity of PKR and to rescue protein synthesis from inhibition by dsRNA. It is notable that sequences in the C-terminal half of the La antigen, including a phosphorylation site at Ser366, which are needed for other regulatory effects of the protein on gene expression are dispensable for the effects of La on PKR. We suggest that La regulates PKR activity solely as a result of its ability to act as an RNA-binding protein that can compete with PKR for limiting amounts of dsRNA.
Animals↗
Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise.
Protein synthesis in skeletal muscle is modulated in response to a variety of stimuli. Two stimuli receiving a great deal of recent attention are increased amino acid availability and exercise. Both of these effectors stimulate protein synthesis in part through activation of translation initiation. However, the full response of translation initiation and protein synthesis to either effector is not observed in the absence of a minimal concentration of insulin. The combination of insulin and either increased amino acid availability or endurance exercise stimulates translation initiation and protein synthesis in part through activation of the ribosomal protein S6 protein kinase S6K1 as well as through enhanced association of eukaryotic initiation factor eIF4G with eIF4E, an event that promotes binding of mRNA to the ribosome. In contrast, insulin in combination with resistance exercise stimulates translation initiation and protein synthesis through enhanced activity of a guanine nucleotide exchange protein referred to as eIF2B. In both cases, the amount of insulin required for the effects is low, and a concentration of the hormone that approximates that observed in fasting animals is sufficient for maximal stimulation. This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle.
Amino Acids↗
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↗
Heat shock-induced translational control of HSP70 and globin synthesis in chicken reticulocytes.
Incubation of chicken reticulocytes at elevated temperatures (43 to 45 degrees C) resulted in a rapid change in the pattern of protein synthesis, characterized by the decreased synthesis of normal proteins, e.g., alpha and beta globin, and the preferential and increased synthesis of only one heat shock protein, HSP70. The repression of globin synthesis was not due to modifications of globin mRNA because the level of globin mRNA and its ability to be translated in vitro were unaffected. The HSP70 gene in reticulocytes was transcribed in non-heat-shocked cells, yet HSP70 was not efficiently translated until the cells had been heat shocked. In non-heat-shocked reticulocytes, HSP70 mRNA was a moderately abundant mRNA present at 1 to 2% of the level of globin mRNA. The rapid 20-fold increase in the synthesis of HSP70 after heat shock was not accompanied by a corresponding increase in the rate of transcription of the HSP70 gene or accumulation of HSP70 mRNA. These results suggest that the elevated synthesis of HSP70 is due to the preferential utilization of HSP70 mRNA in the heat-shocked reticulocyte. The heat shock-induced alterations in the reticulocyte protein-synthetic apparatus were not reversible. Upon return to control temperatures (37 degrees C), heat-shocked reticulocytes continued to synthesize HSP70 at elevated levels whereas globin synthesis continued to be repressed. Despite the presence of HSP70 mRNA in non-heat-shocked reticulocytes, we found that continued transcription was necessary for the preferential translation of HSP70 in heat-shocked cells. Preincubation of reticulocytes with the transcription inhibitor actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole blocked the heat shock-induced synthesis of HSP70. Because the level of HSP70 mRNA was only slightly diminished in cells treated with actinomycin D, we suggest two possible mechanisms for the preferential translation of HSP70 mRNA: the translation of only newly transcribed HSP70 mRNA or the requirement of a newly transcribed RNA-containing factor.
Animals↗
Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control.
Two protein forms of tyrosine phosphatase epsilon (PTPepsilon) are known - receptor-like (tm-PTPepsilon) and non receptor-like (cyt-PTPepsilon), with each form possessing unique tissue-specific expression patterns, subcellular localization, and physiological functions. We describe two additional forms of PTPepsilon protein - p67 and p65. p67 is produced by initiation of translation at an internal initiation codon of PTPepsilon mRNA molecules, while p65 is produced by specific proteolytic cleavage of larger PTPepsilon proteins. Cleavage is inhibited by MG132, but is proteasome-independent. In contrast with full-length tm-PTPepsilon and cyt-PTPepsilon, p67 and p65 are exclusively cytoplasmic, are not phosphorylated by Neu, and do not associate with Grb2 in unstimulated cells. p67 and p65 are catalytically active and can reduce Src-mediated phosphorylation of the Kv2.1 voltage-gated potassium channel, albeit with reduced efficiency which most likely results from their cytoplasmic localization. We also show that full-length cyt-PTPepsilon protein can be found at the cell membrane and in the nucleus and that it is the first 27 residues of cyt-PTPepsilon which determine this localization. p67 and p65 provide mechanisms for removing PTPepsilon activity from the cell membrane, possibly serving to down-regulate PTPepsilon activity there. PTPepsilon emerges as a family of four related proteins whose expression, subcellular localization and most likely physiological roles are subject to complex regulation at the transcriptional, translational and post-translational levels.
3T3 Cells↗
Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis.
The dl331 mutant of adenovirus serotype 5 fails to produce virus-associated (VA) RNAI, and cells infected with this mutant do not synthesize proteins efficiently at late times in infection. The translational defect occurs at the level of polypeptide chain initiation, and cell-free extracts prepared from dl331-infected cells exhibit the defect observed in vivo. Addition of either eukaryotic initiation factor 2 (eIF-2) or guanine nucleotide exchange factor (GEF) to these cell-free extracts restores translational activity, with GEF functioning more efficiently in this regard. These results suggest that cells infected with the dl331 mutant develop a translational block at the level of GEF-catalyzed guanine nucleotide exchange and that this block is most likely established through phosphorylation of the alpha subunit of eIF-2. In the present investigation we show that endogenous HeLa cell GEF activity is significantly reduced in cells infected with the dl331 mutant. Further, in contrast to cells infected with wild-type serotype 2 adenovirus, dl331-infected cells contain increased eIF-2 alpha kinase activity. These results indicate that VA RNAI plays a role in suppressing eIF-2 alpha kinase activity during adenovirus infection of HeLa cells.
Adenoviridae↗
Translational control by the Epstein-Barr virus small RNA EBER-1. Reversal of the double-stranded RNA-induced inhibition of protein synthesis in reticulocyte lysates.
A role for the Epstein-Barr virus small RNA species EBER-1 in the regulation of protein synthesis has been investigated in the reticulocyte-lysate cell-free translation system. Recombinant EBER-1 was synthesized by in vitro transcription of a plasmid containing the viral gene and purified by CF11-cellulose chromatography and ribonuclease III treatment. When added to the reticulocyte lysate at 10-20 micrograms/ml or more, EBER-1 prevents the inhibition of protein synthesis caused by low concentrations of synthetic double-stranded RNA, poly(I).poly(C). This effect is eliminated by treatment of the recombinant EBER-1 with ribonuclease T1. Disruption of the secondary structure of EBER-1 by substitution of inosine for guanosine in the in-vitro-synthesized RNA impairs the ability of EBER-1 to prevent the poly(I).poly(C)-mediated inhibition of protein synthesis. These results suggest that high concentrations of EBER-1 regulate protein synthesis by blocking the activation of the double-stranded RNA-dependent eukaryotic initiation factor 2 alpha (eIF-2 alpha) protein kinase DAI (p68), and that this property is dependent on the secondary structure of the small RNA molecule.
Animals↗
Post-translational control of alcohol dehydrogenase levels in Drosophila melanogaster.
A trans-acting regulatory gene that alters in vivo protein levels of alcohol dehydrogenase (ADH) has been mapped to a region of the third chromosome of Drosophila melanogaster. The gene has been found to affect the in vivo stability of ADH protein. It was not found to alter levels of total protein of two other enzymes assayed. The action of the gene over development and its possible mode of control are discussed.
Alcohol Dehydrogenase↗
Cauliflower Mosaic Virus Gene VI Controls Translation from Dicistronic Expression Units in Transgenic Arabidopsis Plants.
Transformed Arabidopsis plants were used to study the effect of the cauliflower mosaic virus (CaMV) inclusion body protein on translation of dicistronic RNA. Reporter plants contain a dicistronic transcription unit with CaMV open reading frame VII (ORF VII) as the first and the [beta]-glucuronidase (GUS) reporter ORF as the second cistron. "Transactivator plants" contain CaMV ORF VI under the control of the strong CaMV 35S promoter. The transactivator plants were difficult to regenerate and showed an abnormal phenotype. Expression of GUS activity in the reporter plants was very low, but high GUS activity could be induced by introduction of gene VI, either by crossing with plants containing gene VI as a transgene or by infection with CaMV. Histological GUS assays showed that transactivation occurred in all types of tissue and at all developmental stages. The practical implications of the induction of GUS expression from the dicistronic unit by virus infection are discussed.
Journal Article↗
Rotavirus translation control protein takes RNA to heart.
Viruses commonly evolve distinct mechanisms to perform some of the same functions as cells. In the January 11 issue of Cell, Deo et al. describe the structure of rotavirus nonstructural protein 3 in complex with RNA, which explains how it acts as a functional homolog of cellular poly(A) binding protein to promote translation of the nonpolyadenylated rotavirus mRNAs.
Gene Expression Regulation, Viral↗
Overcoming inhibitions. Translational Control sponsored by the Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA, September 13-17, 1989.
Explore the source record for details and available documents.
Animals↗
Post-translational control of occludin membrane assembly in mouse trophectoderm: a mechanism to regulate timing of tight junction biogenesis and blastocyst formation.
The mouse blastocyst forms during the 32-cell stage with the emergence of the blastocoelic cavity. This developmental transition is dependent upon the differentiation and transport function of the trophectoderm epithelium which forms the wall of the blastocyst and exhibits functional intercellular tight junctions (TJs) to maintain epithelial integrity during blastocoele expansion. To investigate mechanisms regulating the timing of blastocyst formation, we have examined the dynamics of expression of occludin, an integral membrane protein of the TJ. Confocal microscopy of intact embryos and synchronised cell clusters revealed that occludin first assembles at the apicolateral membrane contact site between nascent trophectoderm cells usually during the early 32-cell stage, just prior to the time of blastocoele cavitation. This is a late event in the assembly of TJ-associated proteins within trophectoderm which, from our previous data, spans from 8- to 32-cell stages. Occludin membrane assembly is dependent upon prior E-cadherin-mediated cell-cell adhesion and is sensitive to brefeldin A, an inhibitor of Golgi-to-membrane transport. Occludin is delivered to the TJ site in association with the TJ plaque protein, ZO-1(&agr;)+, which we have shown previously is newly transcribed and translated during late cleavage. Immediately after assembly and before cavitation, occludin localised at the TJ site switches from a Triton X-100-soluble to -insoluble form indicative of actin cytoskeletal and/or membrane anchorage. Occludin mRNA and protein are detectable throughout cleavage by RT-PCR and immunoblotting, respectively, indicating that timing of membrane assembly is not controlled by expression alone. Rather, we have identified changes in the pattern of different occludin forms expressed during cleavage which, using phosphatase treatment of embryo lysates, include post-translational modifications. We propose that the phosphorylation of one form of occludin (band 2, 65-67 kDa) during late cleavage, which leads to its exclusive conversion from a Triton X-100-soluble to -insoluble pool, may regulate occludin association with ZO-1(&agr;)+ and membrane assembly, and thereby act to control completion of TJ biogenesis and the timing of blastocyst formation.
Animals↗
Role of amino acids in the translational control of protein synthesis in mammals.
Amino acids, long considered simply substrates for protein synthesis, have been recently shown to act as modulators of intracellular signal transduction pathways typically associated with growth-promoting hormones such as insulin and insulin-like growth factor-1. Many of the endpoints of the signaling pathways regulated by amino acids are proteins involved in mRNA translation. Thus, particular amino acids not only serve as substrates for protein synthesis but are also modulators of the process. The focus of this article is to review recent studies that have used intact animals as experimental models to examine the role of amino acids as modulators of signal transduction pathways.
Amino Acids↗
Intracellular pH and ribosomal protein S6 phosphorylation: role in translational control in Xenopus oocytes.
The induction of amphibian oocyte maturation with progesterone as well as the activation of sea urchin eggs at the time of fertilization result in increased protein synthesis. The increase in both cases involves the recruitment of maternal mRNA onto polysomes. Further, it has been reported that sea urchin eggs, like full-grown Xenopus oocytes, contain no spare translational capacity based on the observation that injected heterologous mRNA is translated only at the expense of endogenous messages. The nature of the limiting component defined by such experiments is not known, but two factors which have been proposed to play a role in regulating protein synthesis are ribosomal protein S6 phosphorylation and intracellular pH. In the current paper, we review the literature and present new evidence on the roles intracellular pH and S6 phosphorylation have in regulating protein synthesis in Xenopus oocytes. We report that pHi does not increase between stage 3 and stage 6, yet the protein synthetic rate increases at least eight fold during the same period. Hence, we conclude that increasing pHi is not a prerequisite for increasing protein synthesis. Moreover, we present three arguments against increased ribosomal protein S6 phosphorylation being sufficient or necessary for increased protein synthesis S6 phosphorylation being sufficient or necessary for increased protein synthesis in Xenopus oocytes. First, the level of S6 phosphorylation does not increase between stages 4 and 6, a period exhibiting a two to three fold increase in protein synthesis. Second, the injection of globin mRNA into stage-4 oocytes increases total protein synthesis two to three fold, but has no effect on S6 phosphorylation. Third, when the injection of globin mRNA into stage-4 oocytes is followed by an injection of MPF, a dramatic increase in S6 phosphorylation is seen, but total protein synthesis is not further stimulated.
Adenosine Triphosphate↗
Translational control of proinsulin synthesis by glucose.
Glucose is known to stimulate proinsulin synthesis in pancreatic islets of rats as well as of many other animals, but the mechanism involved remains uncertain. If proinsulin induction by glucose is regulated at the transcriptional level, the amount of proinsulin mRNA may be increased by the administration of glucose. Alternatively, if proinsulin induction is regulated at the translational level, the rate of proinsulin synthesis may not be correlated with the amount of proinsulin mRNA. We have now used a proinsulin cDNA hybridisation method to determine the amount of proinsulin mRNA and the subcellular distribuation of proinsulin mRNA in rat pancreatic islets. The results suggest that glucose-induced proinsulin synthesis is mainly achieved by enhancing the trnaslation efficiency of proinsulin mRNA preexistent on the membrane-bound polysome in pancreatic islets.
Animals↗
Translational control and differential RNA decay are key elements regulating postsegregational expression of the killer protein encoded by the parB locus of plasmid R1.
The parB locus of plasmid R1, which mediates plasmid stability via postsegregational killing of plasmid-free cells, encodes two genes, hok and sok. The hok gene product is a potent cell-killing protein. The hok gene is regulated at the translational level by the sok gene-encoded repressor, a small anti-sense RNA complementary to the hok mRNA. The hok mRNA is extraordinarily stable, while the sok RNA decays rapidly. The mechanism of postsegregational killing is explained by the following model; the sok RNA molecule rapidly disappears in cells that have lost a parB-carrying plasmid, leading to translation of the stable hok mRNA. Consequently, the Hok protein is synthesized and killing of the plasmid-free cell follows.
Base Sequence↗
Translational control by amino acids and aminoacyl-tRNA synthetases in cultured mammalian cells.
Explore the source record for details and available documents.
Amino Acids↗