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循环RNA的结构和降解调节先天免疫中的PKR激活

Chu-Xiao Liu¹, Xiang Li¹, Fang Nan²

¹State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

|April 30, 2019

概括

循环RNAs (circRNAs) 是稳定的分子,可以抑制先天免疫酶PKR. 它们的降解对于早期免疫反应至关重要, 而它们的减少与SLE等自身免疫性疾病有关.

科学领域:

分子生物学
免疫学
遗传学

背景情况:

循环RNAs (circRNAs) 很丰富,但它们的功能在很大程度上是未知的.
循环RNA具有独特的结构,与线性RNA不同.
它们在先天免疫和自身免疫疾病中的作用是一个新兴的研究领域.

研究的目的:

研究内源性circRNAs在先天免疫中的功能.
探索circRNAs,PKR激活和系统性红斑狼 (SLE) 之间的关系.

主要方法:

分析内源性circRNA结构及其与PKR的相互作用.
在免疫刺激期间研究RNase L的circRNA降解.
在SLE患者的外周血液单核细胞 (PBMC) 中量化circRNA和PKR水平.

主要成果:

内源性circRNAs形成不完美的RNA复合体,并抑制双链RNA (dsRNA) 激活的蛋白激酶 (PKR).
在poly (I: C) 刺激或病毒感染时,circRNAs被RNase L降解,从而促进PKR激活.
患有SLE的患者在PBMC中表现出减少的circRNA和增强的PKR酸化.
在SLE衍生细胞中过度表达dRNAs可以改善异常PKR激活.

结论:

作为PKR的内源抑制剂,circRNAs在先天免疫中发挥着关键作用.
在早期的细胞抗病毒反应中,circRNA降解是一个关键步骤.
循环RNAs和PKR激活的失调与SLE的发病有关.
在SLE等自身免疫性疾病中,circRNA是潜在的治疗点.

关键词:

在PKR 其他类型自体免疫性疾病循环RNA的降解环RNA结构环形RNAs 圆形的RNA 双链RNAs 原生免疫反应系统性红斑狼

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