Zhang Shuxia, Chen Yeru, Wang Yongjie, Zhang Piao, Chen Gang, Zhou Youfa
Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, China.
Front Genet. 2020 Dec 21;11:599548. doi: 10.3389/fgene.2020.599548. eCollection 2020.
Most neurological disorders are caused by abnormal gene translation. Generally, dysregulation of elements involved in the translational process disrupts homeostasis in neurons and neuroglia. Better understanding of how the gene translation process occurs requires detailed analysis of transcriptomic and proteomic profile data. However, a lack of strictly direct correlations between mRNA and protein levels limits translational investigation by combining transcriptomic and proteomic profiling. The much better correlation between proteins and translated mRNAs than total mRNAs in abundance and insufficiently sensitive proteomics approach promote the requirement of advances in translatomics technology. Translatomics which capture and sequence the mRNAs associated with ribosomes has been effective in identifying translational changes by genetics or projections, ribosome stalling, local translation, and transcript isoforms in the nervous system. Here, we place emphasis on the main three translatomics methods currently used to profile mRNAs attached to ribosome-nascent chain complex (RNC-mRNA). Their prominent applications in neurological diseases including glioma, neuropathic pain, depression, fragile X syndrome (FXS), neurodegenerative disorders are outlined. The content reviewed here expands our understanding on the contributions of aberrant translation to neurological disease development.
大多数神经系统疾病是由异常的基因翻译引起的。一般来说，翻译过程中相关元件的失调会破坏神经元和神经胶质细胞的内环境稳态。要更好地理解基因翻译过程是如何发生的，需要对转录组和蛋白质组谱数据进行详细分析。然而，mRNA水平与蛋白质水平之间缺乏严格的直接相关性，限制了通过结合转录组和蛋白质组分析进行的翻译研究。蛋白质与翻译后的mRNA之间在丰度上的相关性比与总mRNA之间的相关性要好得多，且蛋白质组学方法不够灵敏，这就促使人们需要在翻译组学技术上取得进展。捕获并对与核糖体相关的mRNA进行测序的翻译组学，已有效地通过遗传学或预测、核糖体停滞、局部翻译以及神经系统中的转录本异构体来识别翻译变化。在此，我们重点介绍目前用于分析附着于核糖体 - 新生链复合物（RNC - mRNA）的mRNA的三种主要翻译组学方法。概述了它们在包括胶质瘤、神经性疼痛。抑郁症、脆性X综合征（FXS）、神经退行性疾病在内的神经系统疾病中的突出应用。此处综述的内容扩展了我们对异常翻译在神经系统疾病发展中的作用的理解。
