Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 3, Pages 899-903Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201505938
Keywords
nucleobases; peptide nucleic acids; RNA hairpins; translation; triplex formation
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) Supported Program for the Strategic Research Foundation at Private Universities, Japan
- Hirao Taro Foundation of the Konan University Association for Academic Research
- US National Science Foundation [CHE-1406433]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1406433] Funding Source: National Science Foundation
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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 1nm at physiological pH. The triplex formed within the 5 untranslated region of an mRNA reduces the protein expression levels both invitro 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.
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