title: Nucleobase-Modified PNA Suppresses Translation by Forming a Triple Helix with a Hairpin Structure in mRNA In Vitro and in Cells.
abstract: Compounds that bind specifically to double-stranded regions of RNA have potential as regulators of structure-based RNA function; however, sequence-selective recognition of double-stranded RNA is challenging. The modification of peptide nucleic acid (PNA) with unnatural nucleobases enables the formation of PNA-RNA triplexes. Herein, we demonstrate that a 9-mer PNA forms a sequence-specific PNA-RNA triplex with a dissociation constant of less than 1 nm at physiological pH. The triplex formed within the 5' untranslated region of an mRNA reduces the protein expression levels both in vitro and in cells. A single triplet mismatch destabilizes the complex, and in this case, no translation suppression is observed. The triplex-forming PNAs are unique and potent compounds that hold promise as inhibitors of cellular functions that are controlled by double-stranded RNAs, such as RNA interference, RNA editing, and RNA localization mediated by protein-RNA interactions.
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Endoh
authors.affiliation: Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, 13902, USA.
authors.forename: Dziyana
authors.initials: D
authors.lastname: Hnedzko
authors.affiliation: Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, 13902, USA.
authors.forename: Eriks
authors.initials: E
authors.lastname: Rozners
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Japan. sugimoto@konan-u.ac.jp.|Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Kobe, 650-0047, Japan. sugimoto@konan-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
mesh_terms: D066298:In Vitro Techniques; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry*
chemical_list: D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D012313:RNA
keywords: RNA hairpins; nucleobases; peptide nucleic acids; translation; triplex formation