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

被引：636

作者：

Liu, Chu-Xiao ^{[1
]}

Li, Xiang ^{[1
]}

Nan, Fang ^{[2
]}

Jiang, Shan ^{[1
]}

Gao, Xiang ^{[1
,3
]}

Guo, Si-Kun ^{[1
]}

Xue, Wei ^{[2
]}

Cui, Yange ^{[4
]}

Dong, Kaige ^{[2
]}

Ding, Huihua ^{[5
]}

Qu, Bo ^{[5
]}

Zhou, Zhaocai ^{[1
]}

Shen, Nan ^{[4
,5
,6
]}

Yang, Li ^{[2
,3
]}

Chen, Ling-Ling ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Univ Chinese Acad Sci,Shanghai Inst Biochem & Cel, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Univ Chinese Acad Sci,Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[3] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China

[4] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Lab Mol Rheumatol,Shanghai Inst Nutr & Hlth, 320 Yueyang Rd, Shanghai 200031, Peoples R China

[5] Shanghai Jiao Tong Univ, China Australia Ctr Personalized Immunol, Renji Hosp, Shanghai Inst Rheumatol,Sch Med, Shanghai, Peoples R China

[6] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Ctr Autoimmune Genom & Etiol,Dept Pediat, Cincinnati, OH USA

来源：

CELL | 2019年 / 177卷 / 04期

基金：

中国国家自然科学基金;

关键词：

INDUCIBLE GENE-EXPRESSION; PROTEIN-KINASE; READ ALIGNMENT; REVEALS; RECOGNITION; DISEASE; BRAIN; MOUSE; CELLS; DECAY;

D O I：

10.1016/j.cell.2019.03.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：865 / +

页数：37

共 57 条

[1] Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus [J].