Speed controls in translating secretory proteins in eukaryotes--an evolutionary perspective

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Protein translation is a resource-intensive cellular process.
• Translation speed is regulated by tRNA codon usage.
• Existing models do not differentiate translation by free vs. ER-bound ribosomes.

Purpose of the Study:

• To investigate differential translation efficiency based on ribosome type (free vs. ER-bound).
• To identify specific codon patterns associated with different protein destinations.
• To understand the role of codon usage in co- and post-translational protein processing.

Main Methods:

• Comparative analysis of mRNA sequences and codon usage in various organisms (yeast, fly, plant, worm, bovine, human).
• Identification of Signal Peptides (SP) and Transit Peptides (TP).
• Analysis of codon distribution across different protein classes (secreted, membranous, mitochondrial, GPI-anchored).

Main Results:

• Secreted and SP-assisted membranous proteins exhibit N-terminal "slow" tRNA codons followed by "fast" codons.
• Mitochondrial proteins with TPs also show alternating codon patterns.
• GPI-anchored proteins display clusters of low-adapted tRNA codons at their C-termini.
• Specific amino acid and codon selection drives translation demands for the secretory proteome.

Conclusions:

• Differential tRNA codon clusters act as "speed control" signals in mRNA.
• These signals regulate translation to facilitate co- and post-translational processes like membrane translocation, protein processing, and folding.
• Codon usage patterns are crucial for efficient and accurate protein synthesis and maturation, especially for secreted and membrane proteins.