Targeted Degradation of a Hypoxia-Associated Non-coding RNA Enhances the Selectivity of a Small Molecule Interacting with RNA.

ABSTRACT: Small-molecule targeted recruitment of nucleases to RNA is a powerful method to affect RNA biology. Inforna, a sequence-based design approach to target RNA, enables the design of small molecules that bind to and cleave RNA in a selective and substoichiometric manner. Here, we investigate the ability of RNA-targeted degradation to improve the selectivity of small molecules targeting RNA. The microRNA-210 hairpin precursor (pre-miR-210) is overexpressed in hypoxic cancers. Previously, a small molecule (Targapremir-210 [TGP-210]) targeted this RNA in cells, but with a 5-fold window for DNA binding. Appendage of a nuclease recruitment module onto TGP-210 locally recruited ribonuclease L onto pre-miR-210, triggering its degradation. The chimera has enhanced selectivity compared with TGP-210 wit

SUBMITTER: Costales MG 

PROVIDER: S-EPMC6697612 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature