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

被引:782
作者
Li, Xiang [1 ,2 ]
Liu, Chu-Xiao [1 ,2 ]
Xue, Wei [3 ]
Zhang, Yang [1 ,2 ]
Jiang, Shan [1 ,2 ]
Yin, Qing-Fei [1 ,2 ]
Wei, Jia [3 ]
Yao, Run-Wen [1 ,2 ]
Yang, Li [3 ,4 ]
Chen, Ling-Ling [1 ,2 ,4 ]
机构
[1] Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Mol Biol, CAS Ctr Excellence Mol Cell Sci,Shanghai Inst Bio, 320 Yueyang Rd, Shanghai 200031, Peoples R China
[2] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Key Lab Mol Androl, CAS Ctr Excellence Mol Cell Sci,Shanghai Inst Bio, 320 Yueyang Rd, Shanghai 200031, Peoples R China
[3] Univ Chinese Acad Sci, Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci,Key Lab Computat Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China
[4] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
关键词
RNA-PROTEIN INTERACTIONS; MESSENGER-RNA; CIRCULAR RNAS; NONCODING RNAS; BINDING; NF90; PHOSPHORYLATION; MECHANISM; TRANSLATION; REVEALS;
D O I
10.1016/j.molcel.2017.05.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:214 / +
页数:21
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