长链非编码RNA在泛素化、蛋白质降解及人类疾病中的作用
Long noncoding RNAs in ubiquitination, protein degradation, and human diseases
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影响因子:3.1
分区:生物学3区 / 生物物理3区 生化与分子生物学4区
发表日期:2024 Dec
作者:
Prarthana Guha, Avisankar Chini, Ashcharya Rishi, Subhrangsu S Mandal
DOI:
10.1016/j.bbagrm.2024.195061
摘要
蛋白质的稳定性和周转在正常细胞和生理过程中至关重要，其失调可能导致不需要的蛋白积累，引发细胞功能障碍、神经退行性疾病、线粒体功能障碍及代谢紊乱。与蛋白质降解相关的信号机制复杂，研究广泛。许多蛋白酶和酶体系被认为参与调控蛋白降解。尽管如此，我们对蛋白质降解机制的理解仍有限。新兴研究表明，长链非编码RNA（lncRNAs）在多种细胞和生理过程中发挥关键作用，包括代谢、细胞稳态和蛋白质周转。LncRNAs是长度超过200核苷酸的大型核酸，可以与多种蛋白质和核酸相互作用，调节蛋白质结构和功能，从而影响细胞信号转导。LncRNAs广泛存在于不同细胞类型，表现出组织特异性表达，可在血液、尿液等体液中检测到。其表达在多种人类疾病中发生变化，包括癌症、神经系统疾病、免疫紊乱等。LncRNAs逐渐被认为是新型的生物标志物和治疗靶点。本文综述了非编码RNAs（ncRNAs），尤其是长链非编码RNA（lncRNAs）在调控蛋白多泛素化和蛋白酶体降解中的新兴作用。
Abstract
Protein stability and turnover is critical in normal cellular and physiological process and their misregulation may contribute to accumulation of unwanted proteins causing cellular malfunction, neurodegeneration, mitochondrial malfunction, and disrupted metabolism. Signaling mechanism associated with protein degradation is complex and is extensively studied. Many protein and enzyme machineries have been implicated in regulation of protein degradation. Despite these insights, our understanding of protein degradation mechanisms remains limited. Emerging studies suggest that long non-coding RNAs (lncRNAs) play critical roles in various cellular and physiological processes including metabolism, cellular homeostasis, and protein turnover. LncRNAs, being large nucleic acids (>200 nt long) can interact with various proteins and other nucleic acids and modulate protein structure and function leading to regulation of cell signaling processes. LncRNAs are widely distributed across cell types and may exhibit tissue specific expression. They are detected in body fluids including blood and urine. Their expressions are also altered in various human diseases including cancer, neurological disorders, immune disorder, and others. LncRNAs are being recognized as novel biomarkers and therapeutic targets. This review article focuses on the emerging role of noncoding RNAs (ncRNAs), particularly long noncoding RNAs (lncRNAs), in the regulation of protein polyubiquitination and proteasomal degradation.Published by Elsevier B.V.