Abstract
BackgroundGene transcription is regulated by DNA transcriptional regulatory elements, promoters and enhancers that are located outside the coding regions. Here, we examine the characteristic 3-base periodicity of the coding sequences and analyse its correlation with the genome-wide transcriptional profile of yeast.Principal FindingsThe analysis of coding sequences by a new class of indices proposed here identified two different sources of 3-base periodicity: the codon frequency and the codon sequence. In exponentially growing yeast cells, the codon-frequency component of periodicity accounts for 71.9% of the variability of the cellular mRNA by a strong association with the density of elongating mRNA polymerase II complexes. The mRNA abundance explains most of the correlation between the codon-frequency component of periodicity and protein levels. Furthermore, pyrimidine-ending codons of the four-fold degenerate small amino acids alanine, glycine and valine are associated with genes with double the transcription rate of those associated with purine-ending codons.ConclusionsWe demonstrate that the 3-base periodicity of coding sequences is higher than expected by the codon usage frequency (CUF) and that its components, associated with codon bias and amino acid composition, are correlated with gene expression, principally at the level of transcription elongation. This indicates a role of codon sequences in maximising the transcription efficiency in exponentially growing yeast cells. Moreover, the results contrast with the common Darwinian explanation that attributes the codon bias to translational selection by an adjustment of synonymous codon frequencies to the most abundant isoaccepting tRNA. Here, we show that selection on codon bias likely acts at both the transcriptional and translational level and that codon usage and the relative abundance of tRNA could drive each other in order to synergistically optimize the efficiency of gene expression.
Highlights
Gene transcription by the RNA polymerase II machinery is regulated by interactions between transcription factors and specific DNA sites
We demonstrate that the 3-base periodicity of coding sequences is higher than expected by the codon usage frequency (CUF) and that its components, associated with codon bias and amino acid composition, are correlated with gene expression, principally at the level of transcription elongation
The results contrast with the common Darwinian explanation that attributes the codon bias to translational selection by an adjustment of synonymous codon frequencies to the most abundant isoaccepting tRNA
Summary
Gene transcription by the RNA polymerase II machinery is regulated by interactions between transcription factors and specific DNA sites. Transcription factors act before the RNA-elongation stage by binding to the promoter and enhancer DNA regions located outside the coding sequences. Some recent experimental evidence suggests that regulation at the level of transcription elongation in yeast is associated with coding regions. The RTF1 and SPT5 elongation factors and the CHD1 chromatin remodelling factor associate with the coding regions of actively transcribed chromatin, which suggests a regulatory role of chromatin remodelling in transcription elongation [3]. These findings suggest the attractive hypothesis that coding sequences play a regulatory role at the level of transcription elongation. We examine the characteristic 3-base periodicity of the coding sequences and analyse its correlation with the genome-wide transcriptional profile of yeast
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