CHARMING: Harmonizing synonymous codon usage to replicate a desired codon usage pattern.

CHARMING: Harmonizing synonymous codon usage to replicate a desired codon usage pattern.
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迷人:协调同义密码子使用以复制所需的密码子使用模式。

DOI:
10.1002/pro.4223
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发表时间:
2022
期刊:
Protein science : a publication of the Protein Society
影响因子:
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通讯作者:
Clark,PatriciaL
Clark,PatriciaL
中科院分区:
--
文献类型:
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作者:
Wright,Gabriel;Rodriguez,Anabel;Li,Jun;Milenkovic,Tijana;Emrich,ScottJ;Clark,PatriciaL

文献摘要

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越来越多的人认识到,同义密码子的使用,虽然在历史上被认为是表型沉默的,但可以改变与功能性蛋白质产生相关的广泛机制,我们在这里使用这个术语来描述转录(mRNA合成),mRNA半衰期,翻译(蛋白质合成)的净效应以及蛋白质正确折叠成其活性功能结构的概率。特别是,最近的发现强调了次优密码子在修饰共翻译蛋白质折叠中的重要作用。这些结果引起了越来越多的关注编码序列内的同义密码子使用的模式,特别是在发现这些模式可以在同源蛋白质的进化过程中保守。因为同义密码子使用在生物体之间不同,对于异源基因表达,可能需要进行同义密码子取代以匹配异源表达宿主中来自原始生物体的密码子使用模式。在这里,我们提出了CHARMING(密码子协调),一个强大的和通用的算法来设计mRNA序列的异源基因表达和其他相关的密码子协调任务。CHARMING可以作为可下载的Python脚本运行,也可以通过门户网站http://www.codons.org运行。
There is a growing appreciation that synonymous codon usage, although historically regarded as phenotypically silent, can instead alter a wide range of mechanisms related to functional protein production, a term we use here to describe the net effect of transcription (mRNA synthesis), mRNA half‐life, translation (protein synthesis) and the probability of a protein folding correctly to its active, functional structure. In particular, recent discoveries have highlighted the important role that sub‐optimal codons can play in modifying co‐translational protein folding. These results have drawn increased attention to the patterns of synonymous codon usage within coding sequences, particularly in light of the discovery that these patterns can be conserved across evolution for homologous proteins. Because synonymous codon usage differs between organisms, for heterologous gene expression it can be desirable to make synonymous codon substitutions to match the codon usage pattern from the original organism in the heterologous expression host. Here we present CHARMING (for Codon HARMonizING), a robust and versatile algorithm to design mRNA sequences for heterologous gene expression and other related codon harmonization tasks. CHARMING can be run as a downloadable Python script or via a web portal at http://www.codons.org.