Altering the Cleaving Effector in Chimeric Molecules that Target RNA Enhances Cellular Selectivity.

ABSTRACT: Small molecules that target RNA and effect their cleavage are useful chemical probes and potential lead medicines. In this study, we investigate factors affecting degradation of two cancer-associated RNA targets, the mRNA that encodes the transcription factor JUN (c-Jun) and the hairpin precursor to microRNA-372 (pre-miR-372). The two RNA targets harbor the same small-molecule binding site juxtaposed with different neighboring structures. Specifically, pre-miR-372 has AU pairs and contiguous purines on one strand near the small-molecule binding site, making it an ideal substrate for oxidative cleavage via the direct degrader bleomycin A5. In contrast, while JUN mRNA has a similar number of AU pairs near the small-molecule binding site, it lacks contiguous purine nucleotides.

SUBMITTER: Suresh BM 

PROVIDER: S-EPMC10825929 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature