Most proteins in cell and tissue lysates are soluble. We show here that in lysate from human neurons, more than 1,300 proteins are maintained in a soluble and functional state by association with endogenous RNA, as degradation of RNA invariably leads to protein aggregation. The majority of these proteins lack conventional RNA‐binding domains. Using synthetic oligonucleotides, we identify the importance of nucleic acid structure, with single‐stranded pyrimidine‐rich bulges or loops surrounded by double‐stranded regions being particularly efficient in the maintenance of protein solubility. These experiments also identify an apparent one‐to‐one protein‐nucleic acid stoichiometry. Furthermore, we show that protein aggregates isolated from brain tissue from Amyotrophic Lateral Sclerosis patients can be rendered soluble after refolding by both RNA and synthetic oligonucleotides. Together, these findings open new avenues for understanding the mechanism behind protein aggregation and shed light on how certain proteins remain soluble.

中文翻译：

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RNA 的酶促降解导致细胞和组织裂解物中广泛的蛋白质聚集。

细胞和组织裂解物中的大多数蛋白质都是可溶的。我们在这里表明，在来自人类神经元的裂解物中，超过 1,300 种蛋白质通过与内源性 RNA 结合而保持在可溶性和功能性状态，因为 RNA 的降解总是会导致蛋白质聚集。这些蛋白质中的大多数缺乏常规的 RNA 结合结构域。使用合成寡核苷酸，我们确定了核酸结构的重要性，单链富含嘧啶的凸起或被双链区域包围的环在维持蛋白质溶解度方面特别有效。这些实验还确定了明显的一对一蛋白质-核酸化学计量。此外，我们表明，从肌萎缩侧索硬化症患者的脑组织中分离的蛋白质聚集体在被 RNA 和合成寡核苷酸重新折叠后可以变得可溶。总之，这些发现为理解蛋白质聚集背后的机制开辟了新途径，并阐明了某些蛋白质如何保持可溶性。