Nucleobase‐Modified PNA Suppresses Translation by Forming a Triple Helix with a Hairpin Structure in mRNA In Vitro and in Cells |
| |
| Authors: | Dr Tamaki Endoh Dziyana Hnedzko Prof?Dr Eriks Rozners Prof?Dr Naoki Sugimoto |
| |
| Affiliation: | 1. Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Japan;2. Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, USA;3. Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe, Japan |
| |
| 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. |
| |
| Keywords: | nucleobases peptide nucleic acids RNA hairpins translation triplex formation |
|
|
