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Significance Codon bias, the unequal use of synonymous codons to encode amino acids, is known to influence protein expression. Our work finds that codon bias can limit the expression of Toll-like receptor 7, a receptor implicated in autoimmune diseases such as lupus. Surprisingly, we find that the improved protein production associated with codon optimization is not caused by increased translation but instead is caused by an increased rate of transcription. We attribute this change in transcription to increased guanine-cytosine (GC) content following codon optimization. Thus, our work not only addresses a fundamental aspect of immune regulation but also provides mechanistic insight into the controversial issue of how codon bias and GC content influence protein expression.

Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9