Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection
Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection
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病毒感染中与 NF90/NF110 协调的 circRNA 生物发生和功能
DOI：
10.1016/j.molcel.2017.05.023
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发表时间：
2017-07-20
期刊：
影响因子：
16
通讯作者：
Chen, Ling-Ling
中科院分区：
文献类型：
--
作者：
Li, Xiang;Liu, Chu-Xiao;Chen, Ling-Ling
通过反向剪接产生的环状RNA（circRNA）会受到侧翼互补序列的增强。circRNA的表达水平在不同条件下有所差异，这表明蛋白质因子参与了其生物合成过程。我们利用针对所有人类特有基因的全基因组小干扰RNA（siRNA）筛选以及一种高效的circRNA表达报告系统，确定了含有双链RNA结合结构域的免疫因子NF90/NF110是circRNA生物合成的关键调节因子。NF90/NF110通过与环绕形成circRNA的外显子的内含子RNA对相结合，在细胞核中促进circRNA的生成；它们还能在细胞质中与成熟的circRNA相互作用。在病毒感染时，circRNA的表达下降，部分原因是NF90/NF110从细胞核输出到了细胞质。同时，从circRNP复合物中释放出来的NF90/NF110会结合病毒mRNA，这是它们在抗病毒免疫反应中的部分功能。因此，我们的研究结果表明，在病毒感染过程中，NF90/NF110对circRNA的生物合成和功能存在协同调控作用。
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.