The optimization of mRNA expression level by its intrinsic properties -- insights from codon usage pattern and structural stability of mRNA

Abstract

The deviation from the uniform usage of synonymous codons is termed codon usage bias. A lot has been explained from the translational viewpoint for the observed phenomenon. To understand codon usage bias from the transcriptional perspective, we present here a holistic picture of this phenomenon in Saccharomyces cerevisiae, using both wild type and computationally mutated mRNAs. Although in wild type, both codon usage bias and mRNA stability positively regulate the gene (mRNA) expression level and are positively correlated with each other, any deviation from natural situation breaks such equilibrium. Computational examination of mRNA sequences with different sets of synonymous codon composition reveals that in mutated condition, the mRNA expression becomes reduced. Furthermore, constraining codon usage pattern to wild type and carrying out randomization of codons resulted in less stable mRNA. Further, we realized a Boolean Expression explaining the gene expression under various conditions of bias and mRNA stability. These studies suggest that selection of codons is favored for regulation of gene expression through potential formation of messenger RNA structures which contribute to folding stability. The naturally occurring codon composition is responsible for optimization of gene expression, and under such composition, the mRNA structure having highest stability is selected by nature.