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.
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.
Mol Cell. 2017 Jul 20;67(2):214-227.e7. doi: 10.1016/j.molcel.2017.05.023. Epub 2017 Jun 15.
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.
环形 RNA（circRNAs）通过反向剪接产生，其侧翼互补序列增强了 circRNAs 的产生。circRNAs 的表达水平在不同条件下有所变化，这表明蛋白因子参与了它们的生物发生过程。我们使用靶向所有人类独特基因的全基因组 siRNA 筛选和有效的 circRNA 表达报告基因，鉴定出双链 RNA 结合域免疫因子 NF90/NF110 是 circRNA 生物发生的关键调节因子。NF90/NF110 通过与内含子 RNA 对并列的 circRNA 形成外显子结合，在核内促进 circRNA 的产生；它们还在细胞质中与成熟的 circRNA 相互作用。在病毒感染时，circRNA 的表达减少，部分原因是 NF90/NF110 从核内输出到细胞质。同时，从 circRNP 复合物中释放出来的 NF90/NF110 作为其抗病毒免疫反应功能的一部分，与病毒 mRNA 结合。因此，我们的结果表明 NF90/NF110 在病毒感染中对 circRNA 生物发生和功能进行了协调调节。
