Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges.

Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges.
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DOI:
10.1080/15476286.2018.1435248
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发表时间:
2018
期刊:
影响因子:
4.1
通讯作者:
Rossbach O
Rossbach O
中科院分区:
生物学3区
文献类型:
--
作者:
Jost I;Shalamova LA;Gerresheim GK;Niepmann M;Bindereif A;Rossbach O

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环状RNA(CircRNA)是近年来发现的一类新的细胞RNA。据报道,两种circRNA起着分子海绵的作用,隔离特定的microRNA,从而去抑制靶mRNA。由于其与线性RNA相比提高的稳定性,circRNA可能是分子医学和生物学中令人感兴趣的工具。在这项研究中,我们提供了一个原理证明,即circRNA可以被工程化为microRNA海绵。作为一个模型系统,我们使用丙型肝炎病毒(HCV),它需要细胞microRNA-122为其生命周期。我们在体外生产了人工circRNA海绵,有效地隔离microRNA-122,从而抑制HCV细胞培养系统中的病毒蛋白质产生。这些circRNA比它们的线性对应物更稳定,并且定位于细胞质和细胞核,开辟了广泛的潜在应用。
Circular RNAs (circRNAs) were recently described as a novel class of cellular RNAs. Two circRNAs were reported to function as molecular sponges, sequestering specific microRNAs, thereby de-repressing target mRNAs. Due to their elevated stability in comparison to linear RNA, circRNAs may be an interesting tool in molecular medicine and biology. In this study, we provide a proof-of-principle that circRNAs can be engineered as microRNA sponges. As a model system, we used the Hepatitis C Virus (HCV), which requires cellular microRNA-122 for its life cycle. We produced artificial circRNA sponges in vitro that efficiently sequester microRNA-122, thereby inhibiting viral protein production in an HCV cell culture system. These circRNAs are more stable than their linear counterparts, and localize both to the cytoplasm and to the nucleus, opening up a wide range of potential applications.
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