Front Cover: Redirection of miRNA‐Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules (C&B 7/2020),Chemistry & Biodiversity

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Front Cover: Redirection of miRNA‐Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules (C&B 7/2020)
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-07-13 , DOI: 10.1002/cbdv.202000517
Mathias Bolz ₁ , Laura Thomas ₂ , Ute Scheffer ₁ , Elisabeth Kalden ₁ , Roland K. Hartmann ₂ , Michael W. Göbel ₁

Affiliation

Front Cover. Embedded into Argonaute proteins, micro RNAs (miRNAs) form RNA‐induced silencing complexes (RISC) as important negative modulators of translation. Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. In this study, the authors suggest a new concept based on the redirection of RISCs to non‐native target sites. Metabolically stable DNA‐LNA mixmers are used as adaptor molecules to mediate the binding of RISCs to mRNAs without any direct base complementarity. In vitro 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. These findings may represent a first step towards future applications as an alternative to the miRNA replacement approach as reported by Göbel et al. in their full paper at 10.1002/cbdv.202000272.

中文翻译：

封面：通过合成衔接分子将miRNA-Argonaute复合物重定向至特定的靶位（C＆B 7/2020）

前盖。微小RNA（miRNA）嵌入Argonaute蛋白中，形成RNA诱导的沉默复合体（RISC），是重要的翻译负调控因子。miRNA的失调与多种疾病有关，对于这些疾病，将拮抗剂和miRNA替代作为治疗选择进行了讨论。在这项研究中，作者提出了基于RISC重定向到非本地目标站点的新概念。代谢稳定的DNA-LNA混合器用作衔接子分子，介导RISC与mRNA的结合而没有任何直接的碱基互补性。体外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RISC馏分的重定向。这些发现可能代表了Göbel等人报道的替代miRNA替代方法的未来应用的第一步。他们的论文全文为10.1002 / cbdv.202000272。

更新日期：2020-07-13

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