通过定量质谱分析大肠杆菌裂解物中依赖于 RNA 的蛋白质组溶解度维持:等电点、结构紊乱、功能枢纽和伴侣网络方面的蛋白质组特征。

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-02-15 DOI:10.1080/15476286.2024.2315383
Chan Park, Bitnara Han, Yura Choi, Yoontae Jin, Kwang Pyo Kim, Seong Il Choi, Baik L Seong
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引用次数: 0

摘要

蛋白质聚集是错误折叠和蛋白质稳态受损的结果,可导致细胞功能失调,如各种蛋白质病。保护蛋白质在复杂细胞环境中不发生聚集的机制已被研究了很长时间,通常是从以蛋白质为中心的观点出发的。然而,我们的研究让人们深入了解了一个至关重要但却被忽视的角色:RNA。我们发现,耗尽大肠杆菌裂解液中的 RNA 会诱发全局性蛋白质聚集。我们的定量质谱分析从大肠杆菌蛋白质组中发现了 900 多种具有统计学意义的蛋白质,它们的溶解度取决于 RNA。整个蛋白质组的表征显示,RNA依赖性在酸性蛋白质、内在无序蛋白和结构枢纽蛋白中特别富集。此外,我们还观察到依赖 RNA 的酸性蛋白和碱性蛋白在 RNA 结合模式和基因本体论类别上存在明显差异。值得注意的是,关键分子伴侣(触发因子、DnaJ 和 GroES)的溶解度在很大程度上依赖于 RNA,这表明 RNA 型伴侣(称为 chaperna)和蛋白质型伴侣之间存在一种有待探索的层次关系,两者构成了整个伴侣网络。在体内,蛋白质与各种 RNA 稳定或瞬时地结合在一起,这些发现为以 RNA 为中心的维持健康蛋白质组溶解度的作用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RNA-dependent proteome solubility maintenance in Escherichia coli lysates analysed by quantitative mass spectrometry: Proteomic characterization in terms of isoelectric point, structural disorder, functional hub, and chaperone network.

Protein aggregation, a consequence of misfolding and impaired proteostasis, can lead to cellular malfunctions such as various proteinopathies. The mechanisms protecting proteins from aggregation in complex cellular environments have long been investigated, often from a protein-centric viewpoint. However, our study provides insights into a crucial, yet overlooked actor: RNA. We found that depleting RNAs from Escherichia coli lysates induces global protein aggregation. Our quantitative mass spectrometry analysis identified over 900 statistically significant proteins from the Escherichia coli proteome whose solubility depends on RNAs. Proteome-wide characterization showed that the RNA dependency is particularly enriched among acidic proteins, intrinsically disordered proteins, and structural hub proteins. Moreover, we observed distinct differences in RNA-binding mode and Gene Ontology categories between RNA-dependent acidic and basic proteins. Notably, the solubility of key molecular chaperones [Trigger factor, DnaJ, and GroES] is largely dependent on RNAs, suggesting a yet-to-be-explored hierarchical relationship between RNA-based chaperone (termed as chaperna) and protein-based chaperones, both of which constitute the whole chaperone network. These findings provide new insights into the RNA-centric role in maintaining healthy proteome solubility in vivo, where proteins associate with a variety of RNAs, either stably or transiently.

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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
审稿时长
1 months
期刊介绍: RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy
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