Polyamine-mediated regulation of mouse ornithine decarboxylase is posttranslational

1989 ◽  
Vol 9 (12) ◽  
pp. 5484-5490
Author(s):  
T van Daalen Wetters ◽  
M Macrae ◽  
M Brabant ◽  
A Sittler ◽  
P Coffino
Keyword(s):  
Ornithine Decarboxylase ◽  
Translational Regulation ◽  
Feedback Inhibition ◽  
Chimeric Protein ◽  
Sequence Information ◽  
Pulse Label ◽  
Protein Coding ◽  
Coding Sequence ◽  
Series Of Experiments ◽  
The Difference

The activity of ornithine decarboxylase (ODC) is negatively regulated by intracellular polyamines, which thereby mediate a form of feedback inhibition of the initial enzyme in the pathway of their synthesis. This phenomenon has been believed to result, at least in part, from translational regulation. To investigate this further, we performed four series of experiments. First, we found that a chimeric protein encoded by an mRNA containing the ODC 5' leader sequence did not exhibit polyamine-dependent regulation. Second, we showed that transcripts containing the protein-coding sequence of ODC, but no other ODC-derived sequence information, exhibited regulation. Third, we found that the association of ODC mRNA with ribosomes was not altered when intracellular polyamine levels were modulated under conditions previously deemed to cause translational regulation. Last, we carried out experiments to measure the incorporation of [35S]methionine into ODC in polyamine-starved and polyamine-replete cells. Differential incorporation diminished progressively as pulse-label times were shortened; at the shortest labeling time used (4 min), the difference in favor of ODC in polyamine-starved cells was less than twofold. These findings suggest that it is necessary to reevaluate the question of whether polyamines cause alterations of translation of ODC mRNA.

scholarly journals Polyamine-mediated regulation of mouse ornithine decarboxylase is posttranslational.

1989 ◽  
Vol 9 (12) ◽  
pp. 5484-5490 ◽  
Author(s):  
T van Daalen Wetters ◽  
M Macrae ◽  
M Brabant ◽  
A Sittler ◽  
P Coffino
Keyword(s):  
Ornithine Decarboxylase ◽  
Translational Regulation ◽  
Feedback Inhibition ◽  
Chimeric Protein ◽  
Sequence Information ◽  
Pulse Label ◽  
Protein Coding ◽  
Coding Sequence ◽  
Series Of Experiments ◽  
The Difference

The activity of ornithine decarboxylase (ODC) is negatively regulated by intracellular polyamines, which thereby mediate a form of feedback inhibition of the initial enzyme in the pathway of their synthesis. This phenomenon has been believed to result, at least in part, from translational regulation. To investigate this further, we performed four series of experiments. First, we found that a chimeric protein encoded by an mRNA containing the ODC 5' leader sequence did not exhibit polyamine-dependent regulation. Second, we showed that transcripts containing the protein-coding sequence of ODC, but no other ODC-derived sequence information, exhibited regulation. Third, we found that the association of ODC mRNA with ribosomes was not altered when intracellular polyamine levels were modulated under conditions previously deemed to cause translational regulation. Last, we carried out experiments to measure the incorporation of [35S]methionine into ODC in polyamine-starved and polyamine-replete cells. Differential incorporation diminished progressively as pulse-label times were shortened; at the shortest labeling time used (4 min), the difference in favor of ODC in polyamine-starved cells was less than twofold. These findings suggest that it is necessary to reevaluate the question of whether polyamines cause alterations of translation of ODC mRNA.

scholarly journals Translation of ABCE1 Is Tightly Regulated by Upstream Open Reading Frames in Human Colorectal Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 911
Author(s):  
Joana Silva ◽  
Pedro Nina ◽  
Luísa Romão
Keyword(s):  
Translational Regulation ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Leader Sequence ◽  
Open Reading Frames ◽  
Regulatory Function ◽  
Coding Sequence ◽  
Abc Protein ◽  
Upstream Open Reading Frames ◽  
Reading Frames

ATP-binding cassette subfamily E member 1 (ABCE1) belongs to the ABC protein family of transporters; however, it does not behave as a drug transporter. Instead, ABCE1 actively participates in different stages of translation and is also associated with oncogenic functions. Ribosome profiling analysis in colorectal cancer cells has revealed a high ribosome occupancy in the human ABCE1 mRNA 5′-leader sequence, indicating the presence of translatable upstream open reading frames (uORFs). These cis-acting translational regulatory elements usually act as repressors of translation of the main coding sequence. In the present study, we dissect the regulatory function of the five AUG and five non-AUG uORFs identified in the human ABCE1 mRNA 5′-leader sequence. We show that the expression of the main coding sequence is tightly regulated by the ABCE1 AUG uORFs in colorectal cells. Our results are consistent with a model wherein uORF1 is efficiently translated, behaving as a barrier to downstream uORF translation. The few ribosomes that can bypass uORF1 (and/or uORF2) must probably initiate at the inhibitory uORF3 or uORF5 that efficiently repress translation of the main ORF. This inhibitory property is slightly overcome in conditions of endoplasmic reticulum stress. In addition, we observed that these potent translation-inhibitory AUG uORFs function equally in cancer and in non-tumorigenic colorectal cells, which is consistent with a lack of oncogenic function. In conclusion, we establish human ABCE1 as an additional example of uORF-mediated translational regulation and that this tight regulation contributes to control ABCE1 protein levels in different cell environments.

scholarly journals Influence of the Leader protein coding region of foot-and-mouth disease virus on virus replication

2013 ◽  
Vol 94 (7) ◽  
pp. 1486-1495 ◽  
Author(s):  
Graham J. Belsham
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Initiation Codon ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Sequence ◽  
Bhk Cells ◽  
Leader Protein ◽  
Mouth Disease Virus

The foot-and-mouth disease virus (FMDV) Leader (L) protein is produced in two forms, Lab and Lb, differing only at their amino-termini, due to the use of separate initiation codons, usually 84 nt apart. It has been shown previously, and confirmed here, that precise deletion of the Lab coding sequence is lethal for the virus, whereas loss of the Lb coding sequence results in a virus that is viable in BHK cells. In addition, it is now shown that deletion of the ‘spacer’ region between these two initiation codons can be tolerated. Growth of the virus precisely lacking just the Lb coding sequence resulted in a previously undetected accumulation of frameshift mutations within the ‘spacer’ region. These mutations block the inappropriate fusion of amino acid sequences to the amino-terminus of the capsid protein precursor. Modification, by site-directed mutagenesis, of the Lab initiation codon, in the context of the virus lacking the Lb coding region, was also tolerated by the virus within BHK cells. However, precise loss of the Lb coding sequence alone blocked FMDV replication in primary bovine thyroid cells. Thus, the requirement for the Leader protein coding sequences is highly dependent on the nature and extent of the residual Leader protein sequences and on the host cell system used. FMDVs precisely lacking Lb and with the Lab initiation codon modified may represent safer seed viruses for vaccine production.

scholarly journals POSITIONING IMAGES OF SEGMENTED OBJECTS BASED ON QT CROSS-PLATFORM ENVIRONMENT

2020 ◽  
pp. 18-26
Author(s):  
M. E. Golovkin
Keyword(s):  
Scaling Factor ◽  
Single Image ◽  
Image Scaling ◽  
Modern Methods ◽  
Scaling Methods ◽  
Cross Platform ◽  
Series Of Experiments ◽  
The Difference ◽  
Object Features ◽  
Minimum Ratio

The article provides information about the program developed on the basis of the Qt environment, which allows positioning the original image of an object within the field of attention in order to simplify the procedure for generating object features that are invariant to shift, change scale, and rotate its image. Provides an overview of modern methods and software tools for scaling images. The algorithm of the program and a series of computational experiments is described. During the first series, the program positions the image of a triangle within the field of attention using various scaling methods. According to the results of this series, it was concluded which method of scaling an image of an object gives the least loss of quality. In other series of experiments, the program centers and scales the images of a square and a circle inside the attention field with different sizes of the attention field (selection frame) corresponding to a single image scaling factor. Following the results of each series of xperiments, measurements of the sizes of positioned objects were carried out and the dependence of the ratio of their areas on the scaling factor was established. The difference between the maximum and minimum ratio of the coefficients for each series of experiments is calculated. On the basis of the data obtained, it was concluded that for further work with segmented objects of the scene and their positioning in the field of attention, the size of the selection frame of 256x256 pixels can be considered reference.

scholarly journals Insertions and deletions trigger adaptive walks in Drosophila proteins

2012 ◽  
Vol 279 (1740) ◽  
pp. 3075-3082 ◽  
Author(s):  
Evgeny V. Leushkin ◽  
Georgii A. Bazykin ◽  
Alexey S. Kondrashov
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Molecular Adaptation ◽  
Amino Acid Substitutions ◽  
Protein Coding ◽  
Evolution Of Life ◽  
High Fraction ◽  
Adaptive Walks ◽  
The Difference ◽  
Almost All

Maps that relate all possible genotypes or phenotypes to fitness—fitness landscapes—are central to the evolution of life, but remain poorly known. An insertion or a deletion (indel) of one or several amino acids constitutes a substantial leap of a protein within the space of amino acid sequences, and it is unlikely that after such a leap the new sequence corresponds precisely to a fitness peak. Thus, one can expect an indel in the protein-coding sequence that gets fixed in a population to be followed by some number of adaptive amino acid substitutions, which move the new sequence towards a nearby fitness peak. Here, we study substitutions that occur after a frame-preserving indel in evolving proteins of Drosophila . An insertion triggers 1.03 ± 0.75 amino acid substitutions within the protein region centred at the site of insertion, and a deletion triggers 4.77 ± 1.03 substitutions within such a region. The difference between these values is probably owing to a higher fraction of effectively neutral insertions. Almost all of the triggered amino acid substitutions can be attributed to positive selection, and most of them occur relatively soon after the triggering indel and take place upstream of its site. A high fraction of substitutions that follow an indel occur at previously conserved sites, suggesting that an indel substantially changes selection that shapes the protein region around it. Thus, an indel is often followed by an adaptive walk of length that is in agreement with the theory of molecular adaptation.

Sensitization of the gill and siphon withdrawal reflex of Aplysia: multiple sites of change in the neuronal network

1993 ◽  
Vol 70 (3) ◽  
pp. 1210-1220 ◽  
Author(s):  
L. E. Trudeau ◽  
V. F. Castellucci
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neuronal Network ◽  
Feedback Inhibition ◽  
Excitatory Input ◽  
Major Mechanism ◽  
Withdrawal Reflex ◽  
The Difference ◽  
Central Synapses

1. Recent studies have emphasized the major contribution of interneuronal transmission to the mediation and learning-associated modulation of the gill and siphon withdrawal (GSW) reflex of Aplysia. We wish to provide more direct support for the hypothesis that inhibitory junctions are crucial sites of plasticity. 2. In parallel experiments we investigated modulation at five major sites of synaptic transmission in the GSW network: 1) from sensory neurons to motor neurons, 2) from sensory neurons to excitatory interneurons (INTs+) 3) from INTs+ to motor neurons (MNs), 4) from inhibitory interneurons (INTs-) to INTs+, and 5) from INTs+ to INTs-. 3. While recording simultaneously from a single sensory neuron of the LE cluster, an INT+, and a MN, we found that both LE-MN and LE-INTs+ synapses were facilitated by the activation of modulator neurons by stimulation of the left pleuroabdominal connective (185 and 93%, respectively) as well as by serotonin (5-HT) (191 and 84%). Junctions of the second type were therefore less facilitated. The difference in the magnitude of facilitation at these two sites is an indication of a branch-specific, differential efficacy in the modulation of different central synapses made by a single neuron. 4. Although INT(+)-MN junctions have the capacity to display marked posttetanic potentiation, they are not significantly potentiated after connective stimulation. Sensitization of the GSW reflex is therefore not necessarily accompanied by a modification of transmission at these synapses. 5. Inhibitory transmission to INTs+ is significantly reduced by connective stimulation (36%) and by 5-HT (71%). This supports the hypothesis that a reduction of feedback inhibition into INTs+ is a major mechanism of reflex sensitization and may account for the increased evoked firing of INTs+ that is observed after connective stimulation. 6. The excitatory input to INTs- is selectively decreased by 5-HT (50%) and by the molluscan neuropeptide small cardioactive peptide B (38%). This latter effect, which could produce disinhibition of INTs+, may explain the previous observation that this peptide is able to potentiate the evoked input to MNs of the reflex at a concentration (1 microM) that fails to modify monosynaptic sensory-motor transmission. 7. These results indicate that transmission through a small neuronal network that mediates a withdrawal reflex in Aplysia may be modulated at multiple sites and by different mechanisms. These mechanisms include: 1) branch-specific facilitation of sensory neuron outputs and 2) inhibition of INT(-)-INT+ inhibitory postsynaptic potentials by endogenous modulatory neurons and by 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Genome-Wide Detection of Selection Signatures in Duroc Revealed Candidate Genes Relating to Growth and Meat Quality

2020 ◽  
Vol 10 (10) ◽  
pp. 3765-3773
Author(s):  
Jian Yu ◽  
Pengju Zhao ◽  
Xianrui Zheng ◽  
Lei Zhou ◽  
Chuduan Wang ◽  
...  
Keyword(s):  
Growth Rate ◽  
Artificial Selection ◽  
Fast Growth ◽  
Phenotypic Traits ◽  
Sequencing Data ◽  
Selection Signatures ◽  
Protein Coding ◽  
Pig Genome ◽  
The Difference ◽  
Fast Growth Rate

With the development of high-throughput genotyping techniques, selection signatures in the genome of domestic pigs have been extensively interrogated in the last decade. The Duroc, a major commercial pig breed famous for its fast growth rate and high lean ratio, has not been extensively studied focusing on footprints of intensively artificial selection in their genomes by a lot of re-sequencing data. The goal of this study was to investigate genomic regions under artificial selection and their contribution to the unique phenotypic traits of the Duroc using whole-genome resequencing data from 97 pigs. Three complementary methods (di, CLR, and iHH12) were implemented for selection signature detection. In Total, 464 significant candidate regions were identified, which covered 46.4 Mb of the pig genome. Within the identified regions, 709 genes were annotated, including 600 candidate protein-coding genes (486 functionally annotated genes) and 109 lncRNA genes. Genes undergoing selective pressure were significantly enriched in the insulin resistance signaling pathway, which may partly explain the difference between the Duroc and other breeds in terms of growth rate. The selection signatures identified in the Duroc population demonstrated positive pressures on a set of important genes with potential functions that are involved in many biological processes. The results provide new insights into the genetic mechanisms of fast growth rate and high lean mass, and further facilitate follow-up studies on functional genes that contribute to the Duroc’s excellent phenotypic traits.

EFFECTS OF VARIOUS CHEMICAL AND COLD-HARDENING TREATMENTS ON RESISTANCE OF SUGAR BEET SEEDLINGS TO FREEZING

1956 ◽  
Vol 34 (1) ◽  
pp. 154-158
Author(s):  
William G. Corns
Keyword(s):  
Sugar Beet ◽  
Sodium Salt ◽  
Free Acid ◽  
Cold Hardening ◽  
Chemically Treated ◽  
Free Acid Form ◽  
Series Of Experiments ◽  
The Difference ◽  
And Control ◽  
Low Temperature Resistance

Either the free acid form or the sodium salt of Dalapon (2,2-dichloropropionic acid) and of TCA (trichloroacetic acid) and the sodium salt of 2,2,3-trichloropropionic acid (free acid not tested) were effective in improving the low temperature resistance of sugar beet seedlings grown in 4- and 8-p.p.m. solutions in the dark at 21 °C., and evaluated by short exposures to −10 °C. Isopropy-N(3-chlorophenyl) carbamate, amino triazole, sodium chloride, and trichlorobenzoic acid were ineffective in similar tests. In a series of experiments involving periodic sampling and freezing of Dalapon-treated illuminated sugar beet seedlings during a 24 day period of storage at 6 °C., the chemically treated plants were again superior to the comparable controls. The "cold-hardening" treatments tended to increase the magnitude of the difference between chemically treated and control plants. The amount of improvement was more variable in the tests with green plants than with those grown in the dark.

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