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Change in miRNA levels in SH-SY5Y cells after electroporation of peptide nucleic acid (PNA) targeting precursor micro RNA

ABSTRACT: Peptide nucleic acid (PNA) is a neutral DNA analog uniquely suited for triple helical recognition of nucleic acids. However, the practical applications of triplex-forming PNAs have been limited by sequence restrictions, as stable base triples are formed only with purines. Hoogsteen recognition of pyrimidines has been a long-standing challenge. Here, a new approach to improve pyrimidine recognition by enhancing nucleobase stacking in the PNA strand is demonstrated by targeting procursor micro RNA (pre-miRNA). Placing 5-triazolyl uridine adjacent to the modified nucleobases designed for Hoogsteen recognition of pyrimidines in double helical RNA increased the binding affinity while maintaining sequence specificity. The increased binding affinity improved the biological activity of triplex-forming PNAs. RNA-seq analysis targeting mature microRNAs showed that a PNA recognizing a mixed sequence of three nucleobases (G, A, and U) had higher specificity than a similar PNA featuring a uniform purine recognition tract. These results demonstrate a novel strategy to address the issue of pyrimidine recognition, which has been the critical bottleneck for triple helical targeting of nucleic acids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307169 | GEO | 2026/03/05

REPOSITORIES: GEO

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