Selective constraints in yeast genes with differential expressivity: codon pair usage and mRNA stability perspectives

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Protein translation is a fundamental biological process influenced by evolutionary pressures.
• Variations in transfer RNA (tRNA) availability and codon usage impact translation efficiency and accuracy.
• Understanding these factors is crucial for predicting and controlling protein levels.

Purpose of the Study:

• To comprehensively analyze factors guiding protein translation in Saccharomyces cerevisiae.
• To elucidate how diverse factors achieve desired protein levels irrespective of messenger RNA (mRNA) levels.
• To investigate the interplay between tRNA isoacceptor abundance, codon pair context, and mRNA folding stability.

Main Methods:

• Analysis of publicly available mRNA expression and protein abundance data for Saccharomyces cerevisiae.
• Comprehensive examination of tRNA isoacceptor combinations and their correlation with protein levels.
• Assessment of codon pair contextual effects and mRNA secondary structure folding stability.

Main Results:

• Saccharomyces cerevisiae selects specific combinations of abundant and non-abundant tRNA isoacceptors to optimize translation speed and accuracy.
• Strategic positioning of codon pairs, in conjunction with tRNA combinations, influences mRNA secondary structure folding stability.
• Codon pair contextual effects, tRNA abundance, and mRNA folding stability collectively contribute to maintaining translation accuracy and speed.

Conclusions:

• The study identifies key evolutionary constraints and molecular mechanisms governing protein translation in S. cerevisiae.
• Optimized translation speed and accuracy, leading to desired protein levels, are achieved through a combination of tRNA selection and codon context.
• These findings provide insights into the complex regulation of protein homeostasis at the translational level.