Distinct responses to rare codons in select Drosophila tissues.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Allen, SR; Stewart, RK; Rogers, M; Ruiz, IJ; Cohen, E; Laederach, A; Counter, CM; Sawyer, JK; Fox, DT

Published Date

  • May 6, 2022

Published In

Volume / Issue

  • 11 /

PubMed ID

  • 35522036

Pubmed Central ID

  • PMC9116940

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.76893

Language

  • eng

Conference Location

  • England