Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity.
By Chu-Xiao Liu, Xiang Li, Fang Nan, Shan Jiang, Xiang Gao, Si-Kun Guo, Wei Xue, Yange Cui, Kaige Dong, Huihua Ding and 5 more. Cell, 2019
682 citations recorded by the source corpus.
Circular RNAs (circRNAs) produced from back-splicing of exons of pre-mRNAs are widely expressed, but current understanding of their functions is limited. These RNAs are stable in general and are thought to have unique structural conformations distinct from their linear RNA cognates. Here, we show that endogenous circRNAs tend to form 16-26 bp imperfect RNA duplexes and act as inhibitors of double-stranded RNA (dsRNA)-activated protein kinase (PKR) related to innate immunity. Upon poly(I:C) stimulation or viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients with autoimmune disease systemic lupus erythematosus (SLE). Importantly, overexpression of the dsRNA-containing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/728aa4c7383b74c25c05b9cf1509d5ef2d55637a
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- Weiyun Zhou
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- Huai-qiang Ju
- R. Xu
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- Yuli Huang
Citations in the corpus
- Past, present, and future of circRNAs (2019, neutral): “The EMBO Journal 38 : e 100836 | 2019 ª 2019 The Authors The EMBO Journal (Liu et al , 2019).”
- Circular RNA: metabolism, functions and interactions with proteins (2020, background): “Endogenous circRNAs tend to form imperfect duplexes and inhibit PKR (dsRNA-activated protein kinase), while their reduction leads to aberrant PKR activation and autoimmunity [55].”
- Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “PKR circPOLR2A Degradation Systemic lupus erythematosus [15]”