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

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.

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Relationship between ppGpp levels and rates of protein and RNA synthesis in Escherichia coli

Canadian Journal of Biochemistry ◽

10.1139/o76-043 ◽

1976 ◽

Vol 54 (3) ◽

pp. 291-295 ◽

Cited By ~ 2

Author(s):

Gillian Chaloner-Larsson ◽

Hiroshi Yamazaki

Keyword(s):

Escherichia Coli ◽

Protein Synthesis ◽

Amino Acid ◽

Inverse Relationship ◽

Rna Synthesis ◽

Amino Acid Starvation ◽

Cellular Proteins ◽

Mrna Species ◽

Protein And Rna Synthesis ◽

Rna And Protein Synthesis

When amino acid starvation is ended in stringent (relA+) strains of Escherichia coli, the rates of RNA and protein synthesis as well as their accumulation return to normal more slowly in spoT− strains than in the spoT+ strains. The level of ppGpp accumulated declines more slowly in the spoT− strains than in the spoT+ strains. Thus, there is an inverse relationship between ppGpp levels and the rates of RNA and protein synthesis. The slow resumption of protein synthesis in the spoT−relA+ strains could therefore be explained in terms of the limited synthesis of mRNA species coding for the bulk of cellular proteins.

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Multi-step resistance to Chloramphenicol in RC-stringent Escherichia coli K12—its effect on the induction of RNA synthesis by antibiotics under amino acid starvation

Genetics Research ◽

10.1017/s0016672300004171 ◽

1965 ◽

Vol 6 (2) ◽

pp. 304-309 ◽

Cited By ~ 3

Author(s):

E. C. R. Reeve ◽

J. O. Bishop

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Resistant Strain ◽

Parent Strain ◽

Rna Synthesis ◽

Amino Acid Starvation ◽

Sensitive Strain ◽

Escherichia Coli K12 ◽

High Doses

A multi-step Chloramphenicol (CM)-resistant derivative of an RC-stringent strain of Escherichia coli auxotrophic for threonine and leucine was resistant also to Aureomycin (AM) and Puromycin (PM). All three antibiotics released the repression of RNA synthesis due to amino acid starvation in the CM-sensitive parent strain, their relative activities being about 1:10:100 for AM: CM: PM. High doses of AM and CM failed to induce RNA synthesis. The CM-resistant strain required greater concentrations of each antibiotic than the sensitive strain to induce the same level of RNA synthesis, and appeared to be about one hundred times, ten times and five times more resistant to CM, AM and PM, respectively, than the sensitive strain.

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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

Molecular and Cellular Biology ◽

10.1128/mcb.01774-08 ◽

2009 ◽

Vol 29 (10) ◽

pp. 2899-2912 ◽

Cited By ~ 63

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.

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Control of RNA Synthesis by Amino Acids in Landschutz Ascites Tumor Cells

Canadian Journal of Biochemistry ◽

10.1139/o74-123 ◽

1974 ◽

Vol 52 (10) ◽

pp. 867-876 ◽

Cited By ~ 2

Author(s):

Paul Jolicoeur ◽

Fernand Labrie

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Ribosomal Rna ◽

Rna Synthesis ◽

Inhibitory Effect ◽

Amino Acid Starvation ◽

Cytoplasmic Rna ◽

Polysomal Mrna ◽

Deficient Medium ◽

Synthesis And Processing

Landschutz cells incubated in amino acid-deficient medium for 2.5 h show a markedly reduced incorporation of [3H]uridine into 18 S and 28 S cytoplasmic ribosomal RNA (rRNA) and into 28 S, 32 S, and 36 S nuclear RNA measured during the last 90 min of incubation, whereas the radioactivity associated with 45 S pre-rRNA is not affected. Ten-minute pulse-labeling and 15-min pulse-chase experiments show that amino acid starvation inhibits both the synthesis and processing of 45 S pre-rRNA. Amino acid starvation has no significant effect on the labeling of the nucleotide pools. This effect of amino acids was specific for rRNA since the synthesis of 4 S and 5 S cytoplasmic RNA separated on polyacrylamide gels and of polysomal mRNA analyzed on sucrose gradients was not significantly affected during amino acid starvation. These data also indicate that RNA synthesis is non-coordinated in Landschutz cells. Among the 13 amino acids essential for growth of these cells, arginine and glutamine appear to be mainly responsible for the inhibition of synthesis of 18 S and 28 S rRNA measured during incubation in complete amino acid-deficient medium. The removal of any one of the other amino acids has a small inhibitory effect on the incorporation of [3H]uridine into rRNA and their effect on the synthesis of 18 S rRNA is more pronounced than on that of 28 S rRNA. Such effect results in an unbalanced production of these two ribosomal RNA species.

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Effects of amino acid starvation upon constitutive tryptophan messenger RNA synthesis

Journal of Molecular Biology ◽

10.1016/0022-2836(68)90269-6 ◽

1968 ◽

Vol 37 (2) ◽

pp. 303-312 ◽

Cited By ~ 26

Author(s):

John D. Stubbs ◽

Benjamin D. Hall

Keyword(s):

Amino Acid ◽

Messenger Rna ◽

Rna Synthesis ◽

Amino Acid Starvation

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RNA and protein synthetic patterns during germination of Polysphondylium pallidum microcysts

Canadian Journal of Microbiology ◽

10.1139/m78-078 ◽

1978 ◽

Vol 24 (4) ◽

pp. 480-486 ◽

Cited By ~ 6

Author(s):

David I. Gwynne ◽

Danton H. O'Day

Keyword(s):

Molecular Weight ◽

Protein Synthesis ◽

Amino Acid ◽

Rna Synthesis ◽

Leucine Incorporation ◽

Small Molecular Weight ◽

Cellular Slime Mould ◽

Low Level ◽

Polysphondylium Pallidum ◽

Cellular Slime

During microcyst germination in the cellular slime mould Polysphondylium pallidum, an immediate rapid increase in the rate of protein synthesis ([3H]leucine incorporation) is observed within 15 min after the initiation of germination. The data, corrected for amino acid pool changes, reveal that the rate of protein synthesis reaches its peak at [Formula: see text], after which it decreases. A low level of RNA synthesis ([3H]uridine incorporation) is observed after 1 h and this rate increases markedly after 2 h. Analysis of the RNA species shows a low level of synthesis of all ribosomal RNA's which begins between 1 and 2 h and increases after 2 h. The synthesis of a heterogeneously distributed, poly(A)-containingfraction of RNA (presumptive mRNA) is initiated some time after 2 h and the synthesis of a small molecular weight species in the 4–5S region is observed after 3 h. Thus, it seems that Polysphondylium microcysts show sequentially initiated synthesis of RNA during germination.

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Regulation of the Transcription Factor Gcn4 by Pho85 Cyclin Pcl5

Molecular and Cellular Biology ◽

10.1128/mcb.22.15.5395-5404.2002 ◽

2002 ◽

Vol 22 (15) ◽

pp. 5395-5404 ◽

Cited By ~ 53

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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Synthesis of ribonucleic acid in purine-deficient Escherichia coli and a comparison with the effects of amino acid starvation

Biochemical Journal ◽

10.1042/bj1200125 ◽

1970 ◽

Vol 120 (1) ◽

pp. 125-132 ◽

Cited By ~ 4

Author(s):

N. F. Varney ◽

Gillian A. Thomas ◽

K. Burton

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Rna Polymerase ◽

Ribonucleic Acid ◽

Rna Synthesis ◽

Adenine Nucleotides ◽

Amino Acid Starvation ◽

Guanine Nucleotides ◽

Purine Nucleotides ◽

Acid Control

1. Experiments with rifampicin and stringent strains of Escherichia coli (pro−purB−rel+) indicate that purine deficiency does not decrease and may considerably increase the potential for RNA synthesis by RNA polymerase molecules that are bound to DNA and have already commenced transcription. 2. DNA–RNA hybridization experiments indicate that purine starvation increases the distribution of bound RNA polymerase molecules between the cistrons for mRNA and those for stable RNA. 3. Synthesis of β-galactosidase mRNA is more dependent on the ability to synthesize guanine nucleotides than on the ability to synthesize adenine nucleotides. 4. Amino acid starvation tends to decrease the potential for RNA synthesis by RNA polymerase molecules bound to DNA. 5. Since this effect differs from that due to purine starvation, amino acid control of RNA synthesis does not appear to operate solely by causing a deficiency of purine nucleotides. 6. The results are discussed in terms of the ability to initiate RNA chains and to extend them under different circumstances.

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