Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyse the mechanism by which rare codons near the initiation codon inhibit cell growth and protein synthesis, we used the bacteriophage lambda int gene or early codon substitution derivatives. The lambda int gene has a high frequency of rare ATA, AGA and AGG codons; two of them (AGA AGG) located at positions 3 and 4 of the int open reading frame (ORF). Escherichia coli pth (rap) cells, which are defective in peptidyl-tRNA hydrolase (Pth) activity, are more susceptible to the inhibitory effects of int expression as compared with wild-type cells. Cell growth and Int protein synthesis were enhanced by overexpression of Pth and tRNAArg4 cognate to AGG and AGA but not of tRNAIle2a specific for ATA. The increase of Int protein synthesis also takes place when the rare arginine codons AGA and AGG at positions 3 and 4 are changed to common arginine CGT or lysine AAA codons but not to rare isoleucine ATA codons. In addition, overexpression of int in Pth defective cells provokes accumulation of peptidyl-tRNAArg4 in the soluble fraction. Therefore, cell growth and Int synthesis inhibition may be due to ribosome stalling and premature release of peptidyl-tRNAArg4 from the ribosome at the rare arginine codons of the first tandem, which leads to cell starvation for the specific tRNA.
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PMID:The pair of arginine codons AGA AGG close to the initiation codon of the lambda int gene inhibits cell growth and protein synthesis by accumulating peptidyl-tRNAArg4. 1289 27

Translating ribosomes can pass through a stretch of messenger RNA without translating and resume protein chain elongation after the bypassed region. We previously investigated the stimulation of bypassing when the codon in the ribosome [corrected] A-site called for an aminoacyl-tRNA species in short supply. Here, we investigate bypassing in unstarved, growing cells. A collection of lacZ bypass reporters was constructed with nearly all the sense codons as the "takeoff site", each with its matched landing site 16 nucleotides downstream in the beta-galactosidase reading frame. Beta-galactosidase [corrected] synthesis in unstarved cells carrying these reporters was found to vary over a large range. The takeoff sites UUU and AGG yielded unusually high enzyme activities, sufficient for protein sequence analysis; in these cases, sequencing (by Edman degradation or by mass spectrometry) confirmed that the synthesis of lacZ protein occurred through the 16 nt bypass from takeoff to landing site. Thus, bypassing occurs spontaneously under normal conditions, and is not limited to the pathology of amino acid starvation. Indirect evidence suggests that most of the lower enzyme activities of the rest of the collection also reflects bypassing. Another collection of reporters was made with [corrected] various triplets in the A-site [corrected] the codon immediately following a UUC [corrected] takeoff triplet. Spontaneous bypassing in representatives of this collection varied roughly inversely with the abundance of the tRNA encoded at the A-site. For two A-site codons tested, introduction of additional copies of the relevant tRNA gene on a second plasmid reduced spontaneous bypassing. We conclude that any pause with the A-site empty stimulates bypassing. From the P-site and A-site effects on bypassing, we estimated the average frequency of ribosome takeoff; from this, we calculate that the probability that a ribosome will succeed in translating the entire lacZ coding sequence is about 0.73, in agreement with earlier, independent estimates.
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PMID:Spontaneous ribosome bypassing in growing cells. 1589 Jan 94

The open reading frame SUP35 encoding the translation termination eRF3 factor vital to life contains three ATG codons (ATG1, ATG124, and ATG254). Previously, other authors detected two SUP35 transcripts: a major one that corresponds to the full-length open reading frame and a minor transcript that corresponds to the 3' terminal site of SUP35 starting at the third ATG codon (ATG254). In this work, mutations at triplets ATG1, ATG124, and ATG254 were obtained as well as double mutations, which combine the point mutation in one of three ATG triplets and a deletion at the site for binding with the transcription factor Abf1 within the SUP35 (sup35-deltaAbf1) promoter. The influence of these mutations on the yeast viability was analyzed. Mutations at triplets ATG124 and ATG254 did not affect yeast viability in their own right or in the background of deletion sup35-deltaAbf1. Mutation sup35-AGG1 (ATG1-->AGG) causes the lethal effect in cells grown on media containing glucose as the sole source of carbon. The replacement of glucose by galactose, or histidine starvation, partially restore the viability of sup35-AGG1 mutants, but not that of double mutants sup35-deltaAbf1,AGG1. The restoration of sup35-AGG1 mutant viability under these conditions can be explained by either the appearance (or enhancement) of the production of short peptides synthesized on the mRNA triplets SUP35 AUG124 and AUG254, or by the enhanced production of the full-length SUP35 transcript coupled with translation initiation from the noncanonical AGG1 codon. These data confirm that the expression of gene SUP35 at the transcription and(or) translation level is regulated by environmental conditions.
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PMID:[The influence of mutations at ATG triplets of the open reading frame SUP35 on viability of the yeast Saccharomyces cerevisiae]. 1933 11