Redirection of miRNA‐Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules,Chemistry & Biodiversity

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Redirection of miRNA‐Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-06-25 , DOI: 10.1002/cbdv.202000272
Mathias Bolz ₁ , Laura Thomas ₂ , Ute Scheffer ₁ , Elisabeth Kalden ₁ , Roland K Hartmann ₂ , Michael W Göbel ₁

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Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non‐native target sites. Metabolically stable DNA‐LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand. Physical redirection of a dye‐labeled miRNA model and of specific miRNA‐programmed RISC fractions present in HeLa extracts is demonstrated by pull‐down experiments with biotinylated capture oligonucleotides.

中文翻译：

通过合成接头分子将 miRNA-Argonaute 复合物重定向到特定目标位点

miRNA 的失调与多种疾病有关，在这些疾病中，antagomir 和 miRNA 替代被讨论为治疗选择。在这里，我们提出了一个基于 RISC 重定向到非本地目标站点的替代概念。代谢稳定的 DNA-LNA mixmers 用于介导 RISC 与 mRNA 的结合，而与所提供的引导 RNA 链没有任何直接的碱基互补。生物素化捕获寡核苷酸的下拉实验证明了染料标记的 miRNA 模型和 HeLa 提取物中存在的特定 miRNA 编程的 RISC 组分的物理重定向。

更新日期：2020-06-25

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