Differential Synonymous Codon Selection in the B56 Gene Family of PP2A Regulatory Subunits

Abstract

Protein phosphatase 2A (PP2A) functions as a tumor suppressor and consists of a scaffolding, catalytic, and regulatory subunit. The B56 gene family of regulatory subunits impart distinct functions onto PP2A. Codon usage bias (CUB) involves the selection of synonymous codons, which can affect gene expression by modulating processes such as transcription and translation. CUB can vary along the length of a gene, and differential use of synonymous codons can be important in the divergence of gene families. The N-termini of the gene product encoded by B56α possessed high CUB, high GC content at the third codon position (GC3), and high rare codon content. In addition, differential CUB was found in the sequence encoding two B56γ N-terminal splice forms. The sequence encoding the N-termini of B56γ/γ, relative to B56δ/γ, displayed CUB, utilized more frequent codons, and had higher GC3 content. B56α mRNA had stronger than predicted secondary structure at their 5′ end, and the B56δ/γ splice variants had long regions of weaker than predicted secondary structure at their 5′ end. The data suggest that B56α is expressed at relatively low levels as compared to the other B56 isoforms and that the B56δ/γ splice variant is expressed more highly than B56γ/γ.