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长非编码 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.

机构信息

Gene Regulation and Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States of America.

Gene Regulation and Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States of America.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2024 Dec;1867(4):195061. doi: 10.1016/j.bbagrm.2024.195061. Epub 2024 Sep 26.

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.

摘要

蛋白质的稳定性和周转率在正常的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质积累,从而导致细胞功能障碍、神经退行性变、线粒体功能障碍和代谢紊乱。与蛋白质降解相关的信号机制很复杂,并且已经进行了广泛的研究。许多蛋白质和酶机制都与蛋白质降解的调节有关。尽管有这些发现,但我们对蛋白质降解机制的理解仍然有限。新的研究表明,长非编码 RNA(lncRNA)在各种细胞和生理过程中发挥着关键作用,包括代谢、细胞内稳态和蛋白质周转。lncRNA 是长度大于 200nt 的大型核酸,可以与各种蛋白质和其他核酸相互作用,并调节蛋白质结构和功能,从而调节细胞信号转导过程。lncRNA 广泛分布于各种细胞类型中,可能具有组织特异性表达。它们可以在包括血液和尿液在内的体液中检测到。它们的表达在包括癌症、神经紊乱、免疫紊乱在内的各种人类疾病中也发生了改变。lncRNA 被认为是新型生物标志物和治疗靶点。本文综述了非编码 RNA(ncRNA),特别是长非编码 RNA(lncRNA)在调节蛋白质多泛素化和蛋白酶体降解中的新作用。

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