Codon optimality influences homeostatic gene expression in zebrafish.

IF 2.1 3区 生物学 Q3 GENETICS & HEREDITY G3: Genes|Genomes|Genetics Pub Date : 2024-10-24 DOI:10.1093/g3journal/jkae247
Michelle L DeVore, Ariel A Bazzini
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Abstract

The ribosome plays a crucial role in translating mRNA into protein; however, the genetic code extends beyond merely specifying amino acids. Upon translation, codons, the three-nucleotide sequences interpreted by ribosomes, have regulatory properties affecting mRNA stability, a phenomenon known as codon optimality. Codon optimality has been previously observed in vertebrates during embryogenesis, where specific codons can influence the stability and degradation rates of mRNA transcripts. In our previous work, we demonstrated that codon optimality impacts mRNA stability in human cell lines. However, the extent to which codon content influences vertebrate gene expression in vivo remained unclear. In this study, we expand on our previous findings by demonstrating that codon optimality has a robust effect on homeostatic mRNA and protein levels in whole zebrafish during normal physiological conditions. Using reporters with nearly identical nucleotide sequences but different codon compositions, all expressed from the same genomic locus, we show that codon composition can significantly influence gene expression. This study provides new insights into the regulatory roles of codon usage in vertebrate gene expression and underscores the importance of considering codon optimality in genetic and translational research. These findings have broad implications for understanding the complexities of gene regulation and could inform the design of synthetic genes and therapeutic strategies targeting mRNA stability.

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密码子最优性影响斑马鱼的平衡基因表达
核糖体在将 mRNA 翻译成蛋白质的过程中发挥着至关重要的作用;然而,遗传密码的作用并不仅仅局限于指定氨基酸。在翻译过程中,密码子(核糖体解释的三核苷酸序列)具有影响 mRNA 稳定性的调控特性,这种现象被称为密码子最优性。之前在脊椎动物的胚胎发生过程中观察到了密码子最优性,特定的密码子会影响 mRNA 转录本的稳定性和降解率。在我们之前的工作中,我们证明了密码子最优性会影响人类细胞系中 mRNA 的稳定性。然而,密码子内容对脊椎动物体内基因表达的影响程度仍不清楚。在本研究中,我们通过证明密码子优化对正常生理条件下整个斑马鱼体内mRNA和蛋白质水平的稳态影响,进一步拓展了我们之前的发现。通过使用核苷酸序列几乎相同但密码子组成不同的报告基因(均由同一基因组位点表达),我们发现密码子组成可显著影响基因表达。这项研究为了解密码子在脊椎动物基因表达中的调控作用提供了新的视角,并强调了在遗传和转化研究中考虑密码子优化的重要性。这些发现对理解基因调控的复杂性具有广泛的意义,可为设计合成基因和针对 mRNA 稳定性的治疗策略提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
G3: Genes|Genomes|Genetics
G3: Genes|Genomes|Genetics GENETICS & HEREDITY-
CiteScore
5.10
自引率
3.80%
发文量
305
审稿时长
3-8 weeks
期刊介绍: G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights. G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.
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