Triple-Helical Binding of Peptide Nucleic Acid Inhibits Maturation of Endogenous MicroRNA-197.

Triple-Helical Binding of Peptide Nucleic Acid Inhibits Maturation of Endogenous MicroRNA-197.
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DOI:
10.1021/acschembio.1c00133
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发表时间:
2021-07-16
影响因子:
4
通讯作者:
Rozners E
Rozners E
中科院分区:
生物学2区
文献类型:
--
作者:
Endoh T;Brodyagin N;Hnedzko D;Sugimoto N;Rozners E

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序列特异性识别和生物医学相关的双螺旋RNA的功能抑制是非常可取的,但仍然是一个艰巨的问题。目前的研究表明,电穿孔的三链体形成肽核酸(PNA),2-氨基吡啶(M)核碱基修饰,抑制内源性microRNA-197在SH-SY 5 Y细胞的成熟,而对microRNA-155或-27 a的成熟几乎没有影响。体外RNA结合和Dicer抑制试验表明,观察到的生物活性很可能是由于序列特异性PNA-RNA三链体的形成,该三链体抑制了负责微小RNA成熟的内切核酸酶的活性。本研究是使用M修饰的三链体形成PNA调节内源性非编码RNA活性的第一个例子。
Sequence specific recognition and functional inhibition of biomedically relevant double-helical RNAs is highly desirable, but remains a formidable problem. The present study demonstrates that electroporation of a triplex-forming peptide nucleic acid (PNA), modified with 2-aminopyridine (M) nucleobases, inhibited maturation of endogenous microRNA-197 in SH-SY5Y cells, while having little effect on maturation of microRNA-155 or −27a. In vitro RNA binding and Dicer inhibition assays suggested that the observed biological activity was most likely due to a sequence-specific PNA-RNA triplex formation that inhibited the activity of endonucleases responsible for microRNA maturation. The present study is the first example of modulation of activity of endogenous non-coding RNA using M-modified triplex-forming PNA.
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发表时间: 2010-06-30
影响因子: 15
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