scholarly journals RelA-SpoT Homologue toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis

2021 ◽  
Author(s):  
Tatsuaki Kurata ◽  
Tetiana Brodiazhenko ◽  
Sofia Raquel Alves Oliveira ◽  
Mohammad Roghanian ◽  
Kathryn Jane Turnbull ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Bacterial Growth ◽  
Growth Arrest ◽  
Amino Acid Starvation ◽  
Inhibit Protein Synthesis ◽  
Bacterial Physiology ◽  
Mechanism Of Growth ◽  
Synthesis And Degradation ◽  
Do So

RelA-SpoT Homolog (RSH) enzymes control bacterial physiology through synthesis and degradation of the nucleotide alarmone (p)ppGpp. We recently discovered multiple families of Small Alarmone Synthetase (SAS) RSH acting as toxins of toxin-antitoxin (TA) modules, with the FaRel subfamily of toxSAS abrogating bacterial growth by producing an analogue of (p)ppGpp, (pp)pApp. Here we probe the mechanism of growth arrest employed by four experimentally unexplored subfamilies of toxSAS: FaRel2, PhRel, PhRel2 and CapRel. Surprisingly, all these toxins specifically inhibit protein synthesis. To do so, they transfer a pyrophosphate moiety from ATP to the tRNA 3′ CCA. The modification inhibits both tRNA aminoacylation and the sensing of cellular amino acid starvation by the ribosome-associated RSH RelA. Conversely, we show that some Small Alarmone Hydrolase (SAH) RSH enzymes can reverse the pyrophosphorylation of tRNA to counter the growth inhibition by toxSAS. Collectively, we establish RSHs as a novel class of RNA-modifying enzymes.

The effects of D- and L-threo-chloramphenicol on the early development of the chick embryo

Development ◽  
1965 ◽  
Vol 13 (3) ◽  
pp. 341-356
Author(s):  
F. S. Billett ◽  
Rosalba Collini ◽  
Louie Hamilton
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Chick Embryo ◽  
Messenger Rna ◽  
Mammalian Cells ◽  
Animal Cells ◽  
Inhibit Protein Synthesis ◽  
Acid Complex ◽  
Amino Acid Complex ◽  
Bacterial Systems

In many bacterial systems chloramphenicol has been shown to inhibit protein synthesis (Hahn & Wisseman, 1951; Gale & Folkes, 1953). The precise mechanism of this inhibition is not clear, although the evidence suggests that the interaction of the soluble RNA-amino acid complex with the ribosomes is prevented because the attachment of the messenger RNA to the ribosomes is itself impaired (Lacks & Gros, 1959; Nathans & Lipman, 1961; Jardetsky & Julian, 1964; Julian & Jardetsky, 1964). In contrast to its effect on bacterial systems, chloramphenicol has been reported to have little or no action on the protein synthesis by cell-free extracts of mammalian cells (Rendi, 1959; Ehrenstein & Lipmann, 1961). A basis for this resistance has been proposed by Vazquez (1964), who finds that whereas bacterial ribosomes bind chloramphenicol, ribosomes from other organisms do not. Nevertheless, it cannot be stated with any confidence that chloramphenicol has no effect on the protein synthesis of animal cells.

scholarly journals The control of haemoglobin synthesis: factors controlling the output of α and β chains

1969 ◽  
Vol 28 (02) ◽  
pp. 248-254 ◽  
Author(s):  
R. T. Hunt ◽  
A. R. Hunter ◽  
A. J. Munro
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Rna Synthesis ◽  
Amino Acid Starvation ◽  
Control Mechanisms ◽  
Actual Process ◽  
Haemoglobin Synthesis

Analysis of the effects of amino acid starvation in reticulocytes is comparatively simple compared with similar analysis in other tissues of whole organisms. This is mainly because of the absence of RNA synthesis in reticulocytes, but also because the bulk of the protein being synthesized is haemoglobin, a protein whose structure is completely known. The absence of RNA synthesis eliminates complications that would otherwise arise through RNA-mediated control mechanisms which in turn might mask the effects of amino acid starvation on the protein synthetic machinery in the cells (Munro, 1969). Consequently reticulocytes have been used to study the effect of amino acid starvation on the actual process of protein synthesis and assembly.

scholarly journals The hnRNA-Binding Proteins hnRNP L and PTB Are Required for Efficient Translation of the Cat-1 Arginine/Lysine Transporter mRNA during Amino Acid Starvation

2009 ◽  
Vol 29 (10) ◽  
pp. 2899-2912 ◽  
Author(s):  
Mithu Majumder ◽  
Ibrahim Yaman ◽  
Francesca Gaccioli ◽  
Vladimir V. Zeenko ◽  
Chuanping Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Binding Protein ◽  
Mrna Translation ◽  
Amino Acid Starvation ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Polypyrimidine Tract Binding Protein ◽  
Global Protein Synthesis

ABSTRACT The response to amino acid starvation involves the global decrease of protein synthesis and an increase in the translation of some mRNAs that contain an internal ribosome entry site (IRES). It was previously shown that translation of the mRNA for the arginine/lysine amino acid transporter Cat-1 increases during amino acid starvation via a mechanism that utilizes an IRES in the 5′ untranslated region of the Cat-1 mRNA. It is shown here that polypyrimidine tract binding protein (PTB) and an hnRNA binding protein, heterogeneous nuclear ribonucleoprotein L (hnRNP L), promote the efficient translation of Cat-1 mRNA during amino acid starvation. Association of both proteins with Cat-1 mRNA increased during starvation with kinetics that paralleled that of IRES activation, although the levels and subcellular distribution of the proteins were unchanged. The sequence CUUUCU within the Cat-1 IRES was important for PTB binding and for the induction of translation during amino acid starvation. Binding of hnRNP L to the IRES or the Cat-1 mRNA in vivo was independent of PTB binding but was not sufficient to increase IRES activity or Cat-1 mRNA translation during amino acid starvation. In contrast, binding of PTB to the Cat-1 mRNA in vivo required hnRNP L. A wider role of hnRNP L in mRNA translation was suggested by the decrease of global protein synthesis in cells with reduced hnRNP L levels. It is proposed that PTB and hnRNP L are positive regulators of Cat-1 mRNA translation via the IRES under stress conditions that cause a global decrease of protein synthesis.

AMINO ACID CONTROL OF PROTEIN SYNTHESIS AND DEGRADATION IN ISOLATED RAT HEPATOCYTES*

1980 ◽  
Vol 349 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Per O. Seglen ◽  
Anne E. Solheim ◽  
Bjørn Grinde ◽  
Paul B. Gordon ◽  
Per E. Schwarze ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Rat Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Acid Control ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Isolated Rat

scholarly journals INHIBITION OF PROTEIN SYNTHESIS IN NONINFECTED L CELLS BY PARTIALLY PURIFIED INTERFERON PREPARATIONS

1968 ◽  
Vol 36 (3) ◽  
pp. 617-624 ◽  
Author(s):  
Terry C. Johnson ◽  
Michael P. Lerner ◽  
Gerald J. Lancz
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Inhibitory Effect ◽  
Amino Acid Incorporation ◽  
Inhibit Protein Synthesis ◽  
Cell Monolayers ◽  
L Cells ◽  
Acid Incorporation ◽  
L Cell ◽  
Identical Manner

Partially purified interferon preparations, obtained from L-cell monolayers infected with Newcastle disease virus (NDV), were shown to inhibit protein synthesis in noninfected L cells. The incorporation of several amino acids-14C was equally sensitive to the pretreatment of the cells with the interferon preparation. Treatment of L-cell monolayers for 24 hr with 800 units of interferon resulted in a 50% decrease in amino acid incorporation. The degree of inhibition was found to be a function of the interferon concentration and the time of exposure of the cells to the partially purified preparations. No inhibitory effect was detected in medium obtained from noninfected cells and purified in an identical manner. The inhibitory effect was shown to be cell specific in that the partially purified interferon from L cells did not reduce amino acid incorporation in heterospecific cell lines. Heating the interferon preparations at 60°C destroyed their antiviral activity and their ability to inhibit valine-14C incorporation in L cells.

scholarly journals The control of haemoglobin synthesis: factors controlling the output of α and β chains

1969 ◽  
Vol 28 (2) ◽  
pp. 248-254 ◽  
Author(s):  
R. T. Hunt ◽  
A. R. Hunter ◽  
A. J. Munro
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Rna Synthesis ◽  
Amino Acid Starvation ◽  
Control Mechanisms ◽  
Actual Process ◽  
Haemoglobin Synthesis

Analysis of the effects of amino acid starvation in reticulocytes is comparatively simple compared with similar analysis in other tissues of whole organisms. This is mainly because of the absence of RNA synthesis in reticulocytes, but also because the bulk of the protein being synthesized is haemoglobin, a protein whose structure is completely known. The absence of RNA synthesis eliminates complications that would otherwise arise through RNA-mediated control mechanisms which in turn might mask the effects of amino acid starvation on the protein synthetic machinery in the cells (Munro, 1969). Consequently reticulocytes have been used to study the effect of amino acid starvation on the actual process of protein synthesis and assembly.

Control of late G0/G1 progression and protein modification by SmC/IGF I

1987 ◽  
Vol 253 (4) ◽  
pp. C575-C579 ◽  
Author(s):  
N. E. Olashaw ◽  
J. J. Van Wyk ◽  
W. J. Pledger
Keyword(s):  
Amino Acid ◽  
Protein Modification ◽  
Growth Arrest ◽  
Amino Acid Starvation ◽  
Mrna Synthesis ◽  
3T3 Cells ◽  
Somatomedin C ◽  
Future Studies ◽  
Factor I ◽  
Igf I

Somatomedin C/insulin-like growth factor I (SmC/IGF I) mediates traverse of late G0/G1 in density-arrested BALB/c-3T3 cells from a distinct growth arrest point in mid-G0/G1 (the V point) to the initiation of DNA synthesis. As a prelude to future studies aimed at defining the mechanism of action of SmC/IGF I, we investigated the level (e.g., transcriptional, translational) at which SmC/IGF I modulates V to S traverse. The post-V point progression of cells arrested at the V point by amino acid starvation and released into amino acid-replenished medium containing SmC/IGF I, insulin, or platelet-poor plasma (PPP) did not require either mRNA synthesis or an increase in the overall level of protein synthesis. Although two-dimensional gel analysis of proteins prepared from SmC/IGF I-treated cells did not reveal any preferentially synthesized proteins, several SmC/IGF I-induced protein modifications, which result in an increase in isoelectric point (pI) and occur in the absence of mRNA synthesis, were evident. These findings suggest that SmC/IGF I modulates late G0/G1 progression by a posttranscriptional process that may involve protein modification.

scholarly journals Regulation of the Transcription Factor Gcn4 by Pho85 Cyclin Pcl5

2002 ◽  
Vol 22 (15) ◽  
pp. 5395-5404 ◽  
Author(s):  
Revital Shemer ◽  
Ariella Meimoun ◽  
Tsvi Holtzman ◽  
Daniel Kornitzer
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Cellular Protein ◽  
Amino Acid Starvation ◽  
Cyclin Dependent Kinase ◽  
Homeostatic Mechanism ◽  
Metabolic Instability

ABSTRACT The yeast transcription factor Gcn4 is regulated by amino acid starvation at the levels of both protein synthesis and stability. Gcn4 degradation depends on the ubiquitination complex SCFCDC4 and requires phosphorylation by the cyclin-dependent kinase Pho85. Here, we show that Pcl5 is the Pho85 cyclin specifically required for Gcn4 degradation. PCL5 is itself induced by Gcn4 at the level of transcription. However, even when PCL5 is constitutively overexpressed, Pho85-associated Gcn4 phosphorylation activity is reduced in starved cells and Gcn4 degradation is decreased. Under these conditions, the Pcl5 protein disappears because of rapid constitutive turnover. We suggest that, by virtue of its constitutive metabolic instability, Pcl5 may be a sensor of cellular protein biosynthetic capacity. The fact that PCL5 is transcriptionally induced in the presence of Gcn4 suggests that it is part of a homeostatic mechanism that reduces Gcn4 levels upon recovery from starvation.

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