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Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity

Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity

Chu-Xiao Liu, Xiang Li, Fang Nan, Shan Jiang, Xiang Gao, Si-Kun Guo, Wei Xue, Yange Cui, Kaige Dong, Huihua Ding, Bo Qu, Zhaocai Zhou, Nan Shen, Li Yang, Ling-Ling Chen

Cell. 2019 May 2;177(4):865-880.e21.

PMID: 31031002

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP608512976-C	PKR Inhibitor - CAS 608512-97-6		608512-97-6	Price

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