文献类型：期刊文献

英文题名：Codon usage is an important determinant of gene expression levels largely through its effects on transcription

作者：Zhou, Zhipeng[1];Dang, Yunkun[1];Zhou, Mian[1,2];Li, Lin[3];Yu, Chien-hung[1];Fu, Jingjing[1];Chen, She[3];Liu, Yi[1]

机构：[1]Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Natl Inst Biol Sci, Beijing 102206, Peoples R China

年份：2016

卷号：113

期号：41

起止页码：E6117

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000384886900016)】；

基金：We thank Drs. Bing Li, Chen-Ming Chiang, and Shwu-Yuan Wu for helpful discussion; Dr. Qun He for providing the dim-5 KO strains; and the members of our laboratory for technical assistance. This work is supported by National Institutes of Health Grants GM068496, GM084283, and 1R35GM118118 and Welch Foundation Grant I-1560 (to Y.L.).

语种：英文

外文关键词：Neurospora; codon usage; transcription

摘要：Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.