“…Our data provide important insights into developing ligands targeting the tau pre-mRNA hairpin structure. For example, double-stranded RNAs (dsRNAs) may be targeted by chemically modified dsRNA-binding PNAs that show significantly reduced binding to single-stranded RNAs (ssRNAs) [72,74,75,76,77,78] and dsDNAs [72,74,75,76,77,78,79,80,81,82,83]. However, the application of dsRNA-binding PNAs for regulating tau pre-mRNA exon 10 splicing may not be ideal, because the splice site hairpin contains a relatively short dsRNA region (seven base pairs), and residues +5 to +7 (critical for U1 snRNP recognition) are not involved in stable base pairing interactions [21,29,84].…”