Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae

Ian Alexander Williams, Jonathan Paul Richardson, Andrew Starkey, Ian Stansfield

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In-frame stop codons normally signal termination during mRNA translation, but they can be read as 'sense' (readthrough) depending on their context, comprising the 6 nt preceding and following the stop codon. To identify novel contexts directing readthrough, under-represented 5' and 3' stop codon contexts from Saccharomyces cerevisiae were identified by genome-wide survey in silico. In contrast with the nucleotide bias 3' of the stop codon, codon bias in the two codon positions 5' of the termination codon showed no correlation with known effects on stop codon readthrough. However, individually, poor 5' and 3' context elements were equally as effective in promoting stop codon readthrough in vivo, readthrough which in both cases responded identically to changes in release factor concentration. A novel method analysing specific nucleotide combinations in the 3' context region revealed positions +1,2,3,5 and +1,2,3,6 after the stop codon were most predictive of termination efficiency. Downstream of yeast open reading frames (ORFs), further in-frame stop codons were significantly over-represented at the +1, +2 and +3 codon positions after the ORF, acting to limit readthrough. Thus selection against stop codon readthrough is a dominant force acting on 3', but not on 5', nucleotides, with detectable selection on nucleotides as far downstream as +6 nucleotides. The approaches described can be employed to define potential readthrough contexts for any genome.

Original languageEnglish
Pages (from-to)6605-6616
Number of pages11
JournalNucleic Acids Research
Volume32
Issue number22
DOIs
Publication statusPublished - Dec 2004

Keywords

  • read-through
  • drosophila trachea
  • termination codon
  • protein-synthesis
  • nascnt peptide
  • release factors
  • sequence
  • downstream
  • efficiency
  • RNA

Cite this

Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae. / Williams, Ian Alexander; Richardson, Jonathan Paul; Starkey, Andrew; Stansfield, Ian.

In: Nucleic Acids Research, Vol. 32, No. 22, 12.2004, p. 6605-6616.

Research output: Contribution to journalArticle

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AB - In-frame stop codons normally signal termination during mRNA translation, but they can be read as 'sense' (readthrough) depending on their context, comprising the 6 nt preceding and following the stop codon. To identify novel contexts directing readthrough, under-represented 5' and 3' stop codon contexts from Saccharomyces cerevisiae were identified by genome-wide survey in silico. In contrast with the nucleotide bias 3' of the stop codon, codon bias in the two codon positions 5' of the termination codon showed no correlation with known effects on stop codon readthrough. However, individually, poor 5' and 3' context elements were equally as effective in promoting stop codon readthrough in vivo, readthrough which in both cases responded identically to changes in release factor concentration. A novel method analysing specific nucleotide combinations in the 3' context region revealed positions +1,2,3,5 and +1,2,3,6 after the stop codon were most predictive of termination efficiency. Downstream of yeast open reading frames (ORFs), further in-frame stop codons were significantly over-represented at the +1, +2 and +3 codon positions after the ORF, acting to limit readthrough. Thus selection against stop codon readthrough is a dominant force acting on 3', but not on 5', nucleotides, with detectable selection on nucleotides as far downstream as +6 nucleotides. The approaches described can be employed to define potential readthrough contexts for any genome.

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