Department of Cell Biology, Duke University, Durham, United States.
Department of Pharmacology and Cancer Biology, Duke University, Durham, United States.
Elife. 2022 May 6;11:e76893. doi: 10.7554/eLife.76893.
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 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 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 and human testis. We further demonstrate a role for rare codons in an evolutionarily young testis-specific gene, . Optimizing 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.
密码子使用偏好长期以来一直被认为会影响蛋白质的产生。然而，很少有研究分析密码子使用对组织特异性 mRNA 和蛋白质表达的影响。在这里，我们使用密码子修饰的报告基因在 中进行了全基因组筛选，以研究不同组织对密码子使用偏好的反应。这些报告基因揭示了在 内源性表达的基因中，密码子使用稀有性接近极限时，蛋白质表达呈悬崖式下降。然而，在这个极限的边缘，我们发现睾丸和大脑具有独特的能力，可以表达富含稀有密码子的报告基因。我们定义了一个新的组织特异性密码子使用度量标准，组织表观密码子适应指数（taCAI），以揭示 和人类睾丸中内源性表达的基因都存在稀有密码子使用的保守富集。我们进一步证明了稀有密码子在一个进化上年轻的睾丸特异性基因 中的作用。优化 基因的密码子会破坏雌性的生育能力。我们的工作突出了在特定组织中对稀有密码子的不同反应，揭示了密码子偏好在组织生物学中的关键作用。
