Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.76893
Keywords
codon bias; Drosophila; testis; brain; D; melanogaster
Categories
Funding
- American Cancer Society [RSG-128945]
- National Science Foundation
- National Institutes of Health [R01CA94184, P01CA203657, R35GM140844, R01HL111527]
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Codon usage bias plays a critical role in protein production and tissue-specific gene expression. This study investigates the impact of codon usage on tissue-specific mRNA and protein expression using codon-modified reporters in Drosophila melanogaster. The results reveal distinct tissue responses to codon usage bias, with the testis and brain being capable of expressing rare codon-enriched reporters. The findings also demonstrate conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis, highlighting the importance of codon bias in tissue biology.
Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index (taCAI), to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in an evolutionarily young testis-specific gene, RpL10Aa. Optimizing RpL10Aa codons disrupts female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.
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