Small Molecule-Induced Dimerization of Hairpin RNA Interfered with the Dicer Cleavage Reaction
Small Molecule-Induced Dimerization of Hairpin RNA Interfered with the Dicer Cleavage Reaction
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DOI：
10.1021/acs.biochem.0c00920
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发表时间：
2021-01-21
期刊：
影响因子：
2.9
通讯作者：
Nakatani, Kazuhiko
中科院分区：
文献类型：
--
作者：
Murata, Asako;Mori, Yuki;Nakatani, Kazuhiko
MicroRNAs是药物开发的潜在靶点。能够抑制或促进特定miRNA生物发生的小分子将有助于调节其目标基因。到目前为止，各种类型的小分子因其在调节miRNA生物发生方面的潜在应用而被研究。它们与目标初级或前体miRNAs结合，并抑制DROSHA或DICER对这些前体的处理。然而，有效干扰Dever裂解反应的结合部位仍未确定。在这里，我们报道了我们设计的小分子限制性萘啶二聚体(RND)与发夹RNA的发夹环结合并诱导其二聚化。本研究表明，RND与发夹环的结合不能有效地干扰Dier切割反应，但通过RND结合而使发夹RNA二聚化有效地干扰了Dier切割反应。
MicroRNAs are potential targets for drug development. Small molecules that can inhibit or promote a specific miRNA's biogenesis would be useful for regulating its target genes. Various types of small molecules have been investigated so far for their potential application in modulating miRNA biogenesis. They bind to the target primary or precursor miRNAs and inhibit the processing of these precursors by Drosha or Dicer. However, the binding site that effectively interferes with the Dicer cleavage reaction is still undetermined. Here we report that our designed small molecule restricted naphthyridine dimer (RND) binds to the hairpin loop of a hairpin RNA and induces its dimerization. This study shows that the binding of the RND to the hairpin loop was not effective in interfering with the Dicer cleavage reaction, but dimerization of the hairpin RNA by RND binding effectively interfered with the Dicer cleavage reaction.