1. Academic Validation
  2. Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection

Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection

  • Mol Cell. 2017 Jul 20;67(2):214-227.e7. doi: 10.1016/j.molcel.2017.05.023.
Xiang Li 1 Chu-Xiao Liu 1 Wei Xue 2 Yang Zhang 1 Shan Jiang 1 Qing-Fei Yin 1 Jia Wei 2 Run-Wen Yao 1 Li Yang 3 Ling-Ling Chen 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology and 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.
  • 2 Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • 3 Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China. Electronic address: liyang@picb.ac.cn.
  • 4 State Key Laboratory of Molecular Biology and 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; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China. Electronic address: linglingchen@sibcb.ac.cn.
Abstract

Circular RNAs (circRNAs) generated via back-splicing are enhanced by flanking complementary sequences. Expression levels of circRNAs vary under different conditions, suggesting participation of protein factors in their biogenesis. Using genome-wide siRNA screening that targets all human unique genes and an efficient circRNA expression reporter, we identify double-stranded RNA-binding domain containing immune factors NF90/NF110 as key regulators in circRNA biogenesis. NF90/NF110 promote circRNA production in the nucleus by associating with intronic RNA pairs juxtaposing the circRNA-forming exon(s); they also interact with mature circRNAs in the cytoplasm. Upon viral Infection, circRNA expression is decreased, in part owing to the nuclear export of NF90/NF110 to the cytoplasm. Meanwhile, NF90/NF110 released from circRNP complexes bind to viral mRNAs as part of their functions in Antiviral immune response. Our results therefore implicate a coordinated regulation of circRNA biogenesis and function by NF90/NF110 in viral Infection.

Keywords

Alu; ILF3; NF90/NF110; antiviral immune response; circRNA biogenesis; circRNP; complementary sequences.

Figures