(Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation.

IF 4.9 Q1 BIOPHYSICS Biophysical reviews Pub Date : 2023-06-06 eCollection Date: 2023-08-01 DOI:10.1007/s12551-023-01067-4
Yraima Cordeiro, Maria Heloisa O Freire, Adalgisa Felippe Wiecikowski, Mariana Juliani do Amaral
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Abstract

Prion diseases are prototype of infectious diseases transmitted by a protein, the prion protein (PrP), and are still not understandable at the molecular level. Heterogenous species of aggregated PrP can be generated from its monomer. α-synuclein (αSyn), related to Parkinson's disease, has also shown a prion-like pathogenic character, and likewise PrP interacts with nucleic acids (NAs), which in turn modulate their aggregation. Recently, our group and others have characterized that NAs and/or RNA-binding proteins (RBPs) modulate recombinant PrP and/or αSyn condensates formation, and uncontrolled condensation might precede pathological aggregation. Tackling abnormal phase separation of neurodegenerative disease-related proteins has been proposed as a promising therapeutic target. Therefore, understanding the mechanism by which polyanions, like NAs, modulate phase transitions intracellularly, is key to assess their role on toxicity promotion and neuronal death. Herein we discuss data on the nucleic acids binding properties and phase separation ability of PrP and αSyn with a special focus on their modulation by NAs and RBPs. Furthermore, we provide insights into condensation of PrP and/or αSyn in the light of non-trivial subcellular locations such as the nuclear and cytosolic environments.

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(核酸和 RNA 结合蛋白调节朊病毒蛋白和 α-突触核蛋白相分离的(非)功能性见解。
朊病毒病是由一种蛋白质--朊病毒蛋白(PrP)--传播的传染性疾病的原型,目前在分子水平上仍无法理解。聚合的 PrP 可从其单体中产生异源物种。与帕金森病有关的α-突触核蛋白(αSyn)也显示出类似朊病毒的致病特性,同样,PrP 与核酸(NAs)相互作用,进而调节其聚集。最近,我们的研究小组和其他研究小组发现,核酸和/或 RNA 结合蛋白(RBPs)可调节重组 PrP 和/或 αSyn 凝聚物的形成,而不受控制的凝聚可能先于病理聚集。解决神经退行性疾病相关蛋白的异常相分离问题已被认为是一个很有前景的治疗靶点。因此,了解多聚阴离子(如 NAs)在细胞内调节相变的机制,是评估它们在毒性促进和神经元死亡中的作用的关键。在此,我们讨论了有关 PrP 和 αSyn 的核酸结合特性和相分离能力的数据,并特别关注 NAs 和 RBPs 对它们的调节作用。此外,我们还从非三维亚细胞位置(如核和胞浆环境)的角度深入探讨了 PrP 和/或 αSyn 的凝结。
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来源期刊
Biophysical reviews
Biophysical reviews Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
8.90
自引率
0.00%
发文量
93
期刊介绍: Biophysical Reviews aims to publish critical and timely reviews from key figures in the field of biophysics. The bulk of the reviews that are currently published are from invited authors, but the journal is also open for non-solicited reviews. Interested authors are encouraged to discuss the possibility of contributing a review with the Editor-in-Chief prior to submission. Through publishing reviews on biophysics, the editors of the journal hope to illustrate the great power and potential of physical techniques in the biological sciences, they aim to stimulate the discussion and promote further research and would like to educate and enthuse basic researcher scientists and students of biophysics. Biophysical Reviews covers the entire field of biophysics, generally defined as the science of describing and defining biological phenomenon using the concepts and the techniques of physics. This includes but is not limited by such areas as: - Bioinformatics - Biophysical methods and instrumentation - Medical biophysics - Biosystems - Cell biophysics and organization - Macromolecules: dynamics, structures and interactions - Single molecule biophysics - Membrane biophysics, channels and transportation
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