Stable G-quadruplex enabling sequences are selected against by the context-dependent codon bias.

Area of Science:

• Molecular Biology
• Bioinformatics
• Genetics

Background:

• mRNA secondary structures differ between coding regions (CDS) and untranslated regions (UTRs), potentially regulating gene expression and translation efficiency.
• Analyzing secondary structure avoidance due to codon bias is challenging because common structures like hairpins can arise from many sequence combinations.

Purpose of the Study:

• To investigate the impact of codon bias on G-quadruplex (GQ) formation within mRNA coding regions (CDS).
• To determine if specific synonymous codons are selected to avoid stable secondary structures in CDS.

Main Methods:

• Utilized a bioinformatics approach to calculate the frequencies of putative G-quadruplexes (GQs) within the CDS of various species.
• Focused on G-quadruplexes (GQs) as a model secondary structure due to their predictable consensus sequence motifs.

Main Results:

• The most stable G-quadruplexes (GQs) are significantly underrepresented in coding regions (CDS).
• This underrepresentation is achieved through the selective use of specific synonymous codon combinations.
• Identified peptide sequence motifs where silent mutations could lead to stable GQ formation, potentially altering translation.

Conclusions:

• Stable secondary structures, exemplified by G-quadruplexes (GQs), are actively avoided within mRNA coding regions (CDS).
• Synonymous codon usage plays a crucial role in preventing the formation of stable secondary structures, thereby influencing RNA structure-function relationships.
• This provides a comprehensive analysis of secondary structure avoidance in CDS and deepens the understanding of synonymous codon usage implications.