Ghidini A Cléry A Halloy F Allain FHT Hall J 2020 Defects in the functions of RNA binding proteins (RBPs) are at the origin of many diseases, however targeting RBPs with conventional drugs has proven difficult. PROTACs are a new class of drugs that mediate selective degradation of a target protein through a cell's ubiquitylation machinery. PROTACs comprise a moiety that binds the selected protein, conjugated to a ligand of an E3 ligase. Here, we introduce RNA-PROTACs as a new concept in the targeting of RBPs. These chimeric structures employ small RNA mimics as targeting groups that dock the RNA-binding site of the RBP, whereupon a conjugated E3-recruiting peptide derived from the HIF-1α protein directs the RBP for proteasomal degradation. We performed a proof-of-concept with the degradation of two RBPs - a stem cell factor LIN28 and a splicing factor RBFOX1 - and demonstrated their use in cancer cell lines. The RNA-PROTAC approach opens the way to rapid, selective targeting of RBPs in a rational and general fashion. application/pdf https://sonar.ch/global/documents/64672 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.202012330 info:eu-repo/semantics/altIdentifier/pmid/33108679 info:eu-repo/semantics/openAccess Angewandte Chemie (International ed. in English). - 2020 Lin28 PROTAC RNA-binding protein degrader oligonucleotide RNA-PROTACs - degraders of RNA-binding proteins. http://purl.org/coar/resource_type/c_6501