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

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          Abstract

          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 noncoding RNA using M-modified triplex-forming PNA.

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          Author and article information

          Journal
          ACS Chem Biol
          ACS chemical biology
          American Chemical Society (ACS)
          1554-8937
          1554-8929
          Jul 16 2021
          : 16
          : 7
          Affiliations
          [1 ] Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
          [2 ] Department of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United States.
          [3 ] Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
          Article
          NIHMS1762821
          10.1021/acschembio.1c00133
          8670784
          34114795
          beeb27a8-7a1a-447e-abc1-3bf5f4f51e76
          History

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