LC3B-recruiting chimera sends oncogenic pre-miR-21 to the lysosome
- Structure-guided screening of full-length pre-miR-21 picked the kinase inhibitor dovitinib as an RNA binder; binding studies mapped its contacts and modifiable sites.
- Linking it to the LC3B ligand GW5074 gave DPG-3, which bridges RNA and LC3B and routes the RNA to autophagy-lysosome clearance.
- In liver cancer cells DPG-3 beat a dovitinib RiboTAC at lowering pre-miR-21 and miR-21-5p and at curbing proliferation.
💡 Points Based on the abstract
RiboTACs recruit RNase L; this chimera uses the autophagy-lysosome route instead, widening the toolbox for structured RNAs. The convincing next experiment pairs dovitinib-only and GW5074-only controls with lysosome-inhibitor rescue, plus a kinase counter-screen, since dovitinib is a promiscuous ATP-site binder and selectivity over other structured RNAs is untested.
Lysosomal Degradation of MicroRNA-21 Precursor by a Small-Molecule Chimera ↗