Post-translational modifications in stress granule and their implications in neurodegenerative diseases

IF 2.6 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-24 DOI:10.1016/j.bbagrm.2023.194989

Zhangshun Wang , Chen'ang Zhang , Chengyu Fan, Yanfen Liu

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Abstract

Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.

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应激颗粒的翻译后修饰及其在神经退行性疾病中的意义。

应激颗粒（SG）是在应激过程中响应翻译起始抑制而形成的信使核糖核酸和蛋白质。这些动态隔室通过液-液相分离（LLPS）采用流体性质，表现出在细胞环境中不断变化的组成。研究揭示了SG蛋白上发生的一系列翻译后修饰（PTM），它们错综复杂地协调着SG动力学。在神经退行性疾病领域，病理性突变蛋白与许多SG蛋白一起聚集成不溶性聚集体，表现出抵抗分解的弹性。特定的PTM显著地标记这些聚集体，指定它们进行后续降解。通过PTMs对异常SG进行策略性操作是一种很有前途的治疗干预途径。这篇综述发现了最近在理解PTM对LLPS行为和SG组装/拆卸动力学的影响方面取得的进展。通过深入研究PTMs在调节SG动力学中的作用，我们增强了对神经退行性变分子基础的认识。此外，我们为神经退行性疾病的潜在治疗干预靶点提供了宝贵的见解，包括肌萎缩侧索硬化症和额颞叶痴呆等疾病。

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来源期刊

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

44 days

期刊介绍： BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.