Sensing Self and Foreign Circular RNAs by Intron Identity.
Sensing Self and Foreign Circular RNAs by Intron Identity.
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通过内含子身份感知自身和外源环状 RNA。
DOI：
10.1016/j.molcel.2017.05.022
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发表时间：
2017-07-20
期刊：
影响因子：
16
通讯作者：
Chang HY
中科院分区：
文献类型：
--
作者：
Chen YG;Kim MV;Chen X;Batista PJ;Aoyama S;Wilusz JE;Iwasaki A;Chang HY
环状 RNA (circRNA) 是头尾相连的单链 RNA，其功能很大程度上未知。在这里，我们表明，将纯化的体外生成的 circRNA 转染到哺乳动物细胞中，可以有效诱导先天免疫基因，并提供针对病毒感染的保护。核酸传感器 RIG-I 对于感知外源 circRNA 是必需的，并且 RIG-I 和外源 circRNA 在细胞质灶中共聚集。先天免疫的 CircRNA 激活独立于 5' 三磷酸、双链 RNA 结构或外源 circRNA 的一级序列。相反，自我-非自我歧视取决于编程 circRNA 的内含子。使用人类内含子表达外源 circRNA 序列会消除免疫激活，成熟的人类 circRNA 与多种 RNA 结合蛋白相关，反映其内源剪接和生物发生。这些结果揭示了 circRNA 的先天免疫感应，并强调内含子（哺乳动物转录的主要输出）作为自我-非自我身份的仲裁者。陈等人。研究表明，外源性 circRNA 会引发免疫反应，从而预防病毒感染。他们发现细胞根据其生物发生来区分自身和非自身 circRNA。由内源性人类剪接体剪接的 CircRNA 与许多 RNA 结合蛋白结合，这些蛋白将其起源标记为自身分子。
Circular RNAs (circRNAs) are single-stranded RNAs that are joined head to tail with largely unknown functions. Here we show that transfection of purified in vitro generated circRNA into mammalian cells led to potent induction of innate immunity genes and confers protection against viral infection. The nucleic acid sensor RIG-I is necessary to sense foreign circRNA, and RIG-I and foreign circRNA co-aggregate in cytoplasmic foci. CircRNA activation of innate immunity is independent of a 5′ triphosphate, double-stranded RNA structure, or the primary sequence of the foreign circRNA. Instead, self-nonself discrimination depends on the intron that programs the circRNA. Use of a human intron to express a foreign circRNA sequence abrogates immune activation, and mature human circRNA is associated with diverse RNA binding proteins reflecting its endogenous splicing and biogenesis. These results reveal innate immune sensing of circRNA and highlight introns—the predominant output of mammalian transcription—as arbiters of self-nonself identity. Chen et al. show that exogenous circRNAs trigger an immune response that can protect against viral infection. They find that cells distinguish self from nonself circRNAs based on their biogenesis. CircRNAs spliced by endogenous human spliceosomes associate with many RNA-binding proteins that mark their origin as self molecules.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Molinie B;Wang J;Lim KS;Hillebrand R;Lu ZX;Van Wittenberghe N;Howard BD;Daneshvar K;Mullen AC;Dedon P;Xing Y;Giallourakis CC
通讯作者：
Giallourakis CC
DOI：
10.1073/pnas.91.8.3117
发表时间：
1994-04-12
影响因子：
11.1
作者：
FORD, E;ARES, M
通讯作者：
ARES, M
影响因子：
3.7
作者：
Lasda E;Parker R
通讯作者：
Parker R
影响因子：
46.9
作者：
Jeck, William R.;Sharpless, Norman E.
通讯作者：
Sharpless, Norman E.