Rate-limiting steps in yeast protein translation

Area of Science:

• Molecular Biology
• Computational Biology
• Systems Biology

Background:

• Deep sequencing provides detailed ribosome occupancy data on messenger RNAs (mRNAs).
• Understanding translation is crucial for cellular function and protein production.

Purpose of the Study:

• To parameterize a computational model of translation in yeast.
• To determine factors influencing protein yield in transgenes and endogenous genes.
• To infer translation initiation rates for Saccharomyces cerevisiae genes.

Main Methods:

• Leveraging deep sequencing data of ribosome occupancy.
• Developing a computational model tracking ribosomes, transfer RNAs (tRNAs), and mRNAs.
• Analyzing parameter regimes affecting protein yield and inferring initiation rates.

Main Results:

• Identified conditions where fast initiation or high codon bias increase protein yield.
• Inferred yeast gene initiation rates varying by orders of magnitude, correlating with 5' mRNA folding energies.
• Confirmed the 5'-to-3' ramp of decreasing ribosome densities, attributing it to rapid initiation in short genes.

Conclusions:

• Protein production in healthy yeast is typically limited by free ribosome availability.
• During stress, protein production can be enhanced by modulating initiation or elongation rates.
• The study provides insights into the regulation of translation and protein synthesis in yeast.