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Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Identifying Amino Acid Overproducers Using Rare-Codon-Rich Markers

Published on: June 24, 2019

Identification of conserved slow codons that are important for protein expression and function.

Michal Perach¹, Zohar Zafrir², Tamir Tuller^2,3

¹Department of Molecular Microbiology, the Bruce and Ruth Rappaport Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel.

|March 11, 2021

Summary

Slow codons, not just linked to translation speed, play crucial roles in protein folding and function. This study identifies conserved slow codon sites important for protein expression and functional integrity.

Keywords:

Protein translation co-translational folding codon-usage bias computational model evolutionary conservation experimental validation

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Published on: June 24, 2019

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Area of Science:

Molecular Biology
Genetics
Biophysics

Background:

The genetic code's redundancy allows multiple codons for one amino acid, leading to codon usage bias in organisms.
Traditionally, preferred codons were linked to faster translation, while non-preferred codons were associated with slower rates.

Purpose of the Study:

To investigate the role of non-preferred, 'slow' codons in co-translational protein folding and production.
To identify specific locations where slow codons are functionally important and conserved across species.

Main Methods:

Genome-wide analysis of homologous gene groups in divergent bacteria.
Experimental generation of mutants by substituting conserved slow codons with fast codons.
Cellular and biochemical assays to assess protein expression, folding, aggregation, and function.

Main Results:

Identified conserved regions with bias towards slow codons across bacterial species.
Slow-to-fast codon substitutions at specific locations reduced protein expression.
These substitutions also increased protein aggregation and impaired protein function.

Conclusions:

Slow codons have specific roles beyond translation speed, particularly in regulating co-translational protein folding.
Conserved slow codons are critical for efficient protein production, proper folding, and overall protein function.
The study provides a method to identify functionally relevant slow codon regions.