Stabilizing non-native excited states as a therapeutic strategy for targeting RNA [article]

Laura R Ganser, Chia-Chieh Chu, Hal P Bogerd, Megan L Kelly, Bryan R Cullen, Hashim M Al-Hashimi
2019 bioRxiv   pre-print
Regulatory RNAs transiently morph into non-native high-energy "excited" conformational states that remodel the native ground state secondary structure needed for function. For two HIV-1 regulatory RNAs, we show that stabilizing excited states using point substitution mutations leads to potent conformation-dependent inhibition of RNA cellular activity to a degree that correlates with the extent of excited state stabilization. Stabilizing non-native excited states potentially provides a general
more » ... rovides a general therapeutic strategy for targeting RNA.
doi:10.1101/634576 fatcat:ps6lailprze47efecn5lvj7r2y