期刊
CELL
卷 177, 期 4, 页码 865-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.03.046
关键词
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资金
- Chinese Academy of Sciences (CAS) [XDB19020104]
- Ministry of Science and Technology of China [2016YFA0100701]
- National Natural Science Foundation of China (NSFC) [91440202, 31821004, 31725009]
- Howard Hughes Medical Institute International Program [55008728]
- NSFC [31801073, 31730111, 81401331, 31630021]
- Youth Innovation Promotion Association CAS
- Shanghai Sailing Program
Circular RNAs (circRNAs) produced from backsplicing 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.
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