Codon usage biases are found in all genomes and influence protein expression levels. The codon usage effect on protein expression was thought to be mainly due to its impact on translation. Here, we show that transcription termination is an important driving force for codon usage bias in eukaryotes. Using Neurospora crassa as a model organism, we demonstrated that introduction of rare codons results in premature transcription termination (PTT) within open reading frames and abolishment of full-length mRNA. PTT is a wide-spread phenomenon in Neurospora, and there is a strong negative correlation between codon usage bias and PTT events. Rare codons lead to the formation of putative poly(A) signals and PTT. A similar role for codon usage bias was also observed in mouse cells. Together, these results suggest that codon usage biases co-evolve with the transcription termination machinery to suppress premature termination of transcription and thus allow for optimal gene expression.

中文翻译：

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密码子使用偏好与转录终止机制共同进化，以抑制过早切割和聚腺苷酸化

密码子使用偏好存在于所有基因组中并影响蛋白质表达水平。密码子使用对蛋白质表达的影响被认为主要是由于其对翻译的影响。在这里，我们表明转录终止是真核生物中密码子使用偏倚的重要驱动力。使用粗糙脉孢菌作为模式生物，我们证明了稀有密码子的引入导致开放阅读框架内的过早转录终止 (PTT) 和全长 mRNA 的消除。PTT是Neurospora中广泛存在的现象，密码子使用偏向与PTT事件之间存在很强的负相关。稀有密码子导致推定的 poly(A) 信号和 PTT 的形成。在小鼠细胞中也观察到密码子使用偏倚的类似作用。一起，