The deamination of adenosine to inosine by RNA editing is a widespread post-transcriptional process that expands genetic diversity. Selective substitution of inosine for adenosine in pre-mRNA transcripts can alter splicing, mRNA stability, and the amino acid sequence of the encoded protein. The functional consequences of RNA editing-dependent amino acid substitution are known for only a handful of RNA editing substrates. Many of these studies began in heterologous mammalian expression systems; however, the gold-standard for determining the functional significance of transcript-specific re-coding A-to-I editing events is the generation of a mouse model that expresses only one RNA editing-dependent isoform. The frequency of site-specific RNA editing varies spatially, temporally, and in some diseases, therefore, determining the profile of RNA editing frequency is also an important element of research. Here we review the strengths and weaknesses of existing mouse models for the study of RNA editing, as well as methods for quantifying RNA editing frequencies in vivo. Importantly, we highlight opportunities for future RNA editing studies in mice, projecting that improvements in genome editing and high-throughput sequencing technologies will allow the field to excel in coming years.

中文翻译：

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使用小鼠模型解开非同义 RNA 编辑的秘密

通过 RNA 编辑将腺苷脱氨基为肌苷是一种广泛的转录后过程，可扩大遗传多样性。在前 mRNA 转录物中用肌苷选择性取代腺苷可以改变剪接、mRNA 稳定性和编码蛋白质的氨基酸序列。仅少数 RNA 编辑底物已知依赖于 RNA 编辑的氨基酸取代的功能后果。许多这些研究始于异源哺乳动物表达系统；然而，确定转录本特异性重新编码 A-to-I 编辑事件的功能意义的黄金标准是生成只表达一种依赖于 RNA 编辑的同种型的小鼠模型。位点特异性 RNA 编辑的频率随空间、时间和某些疾病而变化，因此，确定 RNA 编辑频率的概况也是研究的一个重要元素。在这里，我们回顾了用于研究 RNA 编辑的现有小鼠模型的优缺点，以及量化体内 RNA 编辑频率的方法。重要的是，我们强调了未来小鼠 RNA 编辑研究的机会，预计基因组编辑和高通量测序技术的改进将使该领域在未来几年取得优异成绩。