Codon specificity of starvation induced misreading

Johnston, Timothy C.; Borgia, Peter T.; Parker, Jack

doi:10.1007/bf00341447

Cited by 49 publications

(30 citation statements)

References 21 publications

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“…Clearly, the abundance of suppressor activity in natural bacterial populations (17), as well as the use of a termination codon to encode selenocysteine (18), require that termination be context-dependent. Similar context effects have been shown to influence the fidelity of translation (19,20) as well as the efficiency of translation initiation (21)(22)(23).…”

mentioning

confidence: 63%

Nonrandom utilization of codon pairs in Escherichia coli.

Gutman

Hatfield

1989

Proc. Natl. Acad. Sci. U.S.A.

250

226

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We have analyzed protein-coding sequences of Escherichia coli and find that codon-pair utilization is highly biased, reflecting overrepresentation or underrepresentation of many pairs compared with their random expectations. This effect is over and above that contributed by nonrandomness in the use of amino acid pairs, which itself is highly evident; it is much weaker when nonadjacent codon pairs are examined and virtually disappears when pairs separated by two or three intervening codons are evaluated. There appears to be a high degree of directionality in this bias: any codon that participates in many nonrandom pairs tends to make both over-and underrepresented pairs, but preferentially as a left-or righthand member. We show a relationship between codon-pair utilization patterns and levels of gene expression: genes encoding proteins expressed at high levels tend to contain more abundant, but more highly underrepresented, codon pairs, relative to genes expressed at low levels. The nonrandom utilization of codon pairs may be a consequence of their effects on translational efficiency, which in turn may be related to the compatibility of adjacent aminoacyl-tRNA isoacceptors at the A and P sites of a translating ribosome.

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mentioning

confidence: 63%

Nonrandom utilization of codon pairs in Escherichia coli.

Gutman

Hatfield

1989

Proc. Natl. Acad. Sci. U.S.A.

250

226

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“…Depending on the severity of the starvation, the error rate may increase by an order of magnitude in stringent cells, and two orders of magnitude in relaxed ( relA − ) cells. 7,81 The increased error rate occurs mainly because competing near-cognate tRNAs get access to deliver their amino acids to ribosomes stalled at the “hungry” codons, due to a shortage of cognate tRNA charged with the amino acid starved for. 7,8,81 We consider it highly plausible that degradation of the vacant tRNA pool is important for reducing the translational error-frequency because it would reduce the amount of competing near-cognate charged tRNA.…”

Section: Why Degrade Trna?mentioning

confidence: 99%

“…7,81 The increased error rate occurs mainly because competing near-cognate tRNAs get access to deliver their amino acids to ribosomes stalled at the “hungry” codons, due to a shortage of cognate tRNA charged with the amino acid starved for. 7,8,81 We consider it highly plausible that degradation of the vacant tRNA pool is important for reducing the translational error-frequency because it would reduce the amount of competing near-cognate charged tRNA. The reduction in tRNA levels upon amino acid starvation is a combined effect of the ppGpp-mediated halt in tRNA synthesis and the degradation of already existing tRNA molecules.…”

Section: Why Degrade Trna?mentioning

confidence: 99%

Transfer RNA instability as a stress response inEscherichia coli: Rapid dynamics of the tRNA pool as a function of demand

2018

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Production of the translation apparatus of E. coli is carefully matched to the demand for protein synthesis posed by a given growth condition. For example, the fraction of RNA polymerases that transcribe rRNA and tRNA drops from 80% during rapid growth to 24% within minutes of a sudden amino acid starvation. We recently reported in Nucleic Acids Research that the tRNA pool is more dynamically regulated than previously thought. In addition to the regulation at the level of synthesis, we found that tRNAs are subject to demand-based regulation at the level of their degradation. In this point-of-view article we address the question of why this phenomenon has not previously been described. We also present data that expands on the mechanism of tRNA degradation, and we discuss the possible implications of tRNA instability for the ability of E. coli to cope with stresses that affect the translation process.

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“…After a temperature shift to 40°C, peptidyl-tRNA accumulation begins, and less and less tRNA remains available for continued protein synthesis. There is ample evidence that depletion of a tRNA species leads to increased misreading of its corresponding codon(s) (6,8,9,(18)(19)(20). Misreading could keep protein synthesis going for a while at the expense of increased error rates.…”

Section: Discussionmentioning

confidence: 99%

Effect of a 2-methylthio-N6-isopentenyladenosine deficiency on peptidyl-tRNA release in Escherichia coli

Petrullo¹,

Elseviers²

1986

J Bacteriol

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We examined the effect of miaA, a mutation conferring a deficiency in 2-methylthio-N6-isopentenyladenosine in tRNA, on patterns of peptidyl-tRNA accumulation in Escherichia coli strains deficient in peptidyl-tRNA hydrolase activity. A specific reduction in peptidyl-tRNA accumulation was seen for tRNAs which normally contain the 2-methylthio-N6-isopentenyladenosine modification. These results provide new evidence in support of the ribosome editor model, which links peptidyl-tRNA release to mistranslation events.The isolation of a temperature-sensitive mutation in an Escherichia coli gene coding for peptidyl-tRNA hydrolase (pth) was reported by Atherly and Menninger in 1972 (1). This enzyme specifically cleaves peptides from cytoplasmic peptidyl-tRNA. The pth mutation is conditionally lethal (16). This implies that peptidyl-tRNA hydrolase is an essential enzyme in E. coli. Yet, in the classical description of protein synthesis, there is no step where cytoplasmic peptidyl-tRNA is generated. In addition, the release of a nonfunctional, half-finished peptide from the ribosome seems extremely wasteful.These considerations led Menninger (11) to propose that the release of peptidyl-tRNA is associated with a proofreading mechanism, the so-called ribosome editor. In this model, the premature release of peptidyl-tRNA is the result of an active editing mechanism which recognizes and specifically releases noncognate tRNA molecules that have escaped proofreading in the acceptor (A) site (23). Recent evidence suggests that peptidyl-tRNA release is associated with the translocation step (15).The ribosome editor hypothesis leads to a very precise prediction. The vast majority of, if not all, tRNA molecules released as peptidyl-tRNA should be noncognate; i.e., they should have been released in the process of mistranslating a codon. However, testing this precise prediction directly has proven difficult (2, 3).Here we describe a new approach to test the ribosome editor hypothesis. We previously studied the effect of miaA, a mutation which causes a deficiency in 2-methylthio-N6-isopentenyladenosine in tRNA, on the readthrough and suppression of nonsense mutations in E. coli (21). This modification in 2-methylthio-N6-isopentenyladenosine, hereafter called isopentenyladenosine, occurs 3' adjacent to the anticodon in all tRNAs that read codons beginning with uracil (17). Those rely ,more heavily on tRNA modifications such as the isopentenyladenosine modification for stabilization in the A site of a programmed ribosome.The miaA mutation can be used to tag genetically a subpopulation of tRNAs. Based on our previous results, introduction of the miaA allele should specifically reduce the ability of miaA tRNAs to misread other codons but leave all other aspects of protein synthesis more or less unaltered. Here we report how the miaA mutation influenced patterns of peptidyl-tRNA release. Our approach had the advantage that the ribosome and therefore the ribosome editor remained unaltered throughout these experiments. modification was also ...

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Codon specificity of starvation induced misreading

Cited by 49 publications

References 21 publications

Nonrandom utilization of codon pairs in Escherichia coli.

Nonrandom utilization of codon pairs in Escherichia coli.

Transfer RNA instability as a stress response inEscherichia coli: Rapid dynamics of the tRNA pool as a function of demand

Effect of a 2-methylthio-N6-isopentenyladenosine deficiency on peptidyl-tRNA release in Escherichia coli

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