Antiprion Drugs Target Ribosomal RNA Activity
Author Information
Author(s): Déborah Tribouillard-Tanvier, Suzana Dos Reis, Fabienne Gug, Cécile Voisset, Vincent Béringue, Raimon Sabate, Ema Kikovska, Nicolas Talarek, Stéphane Bach, Chenhui Huang, Nathalie Desban, Sven J. Saupe, Surachai Supattapone, Jean-Yves Thuret, Stéphane Chédin, Didier Vilette, Hervé Galons, Suparna Sanyal, Marc Blondel
Primary Institution: INSERM U613, Brest, France
Hypothesis
Can 6-aminophenanthridine (6AP) and Guanabenz (GA) selectively inhibit the protein folding activity of the ribosome without affecting protein synthesis?
Conclusion
6AP and GA are the first compounds shown to selectively inhibit the protein folding activity of the ribosome without affecting its protein synthesis function.
Supporting Evidence
- 6AP and GA were isolated as antiprion drugs using a yeast-based assay.
- Both drugs specifically inhibit the ribosomal RNA-mediated protein folding activity.
- Neither drug affects the peptidyl transferase activity of the ribosome.
- 6AP and GA do not interact directly with prion proteins.
- Binding of ribosomal proteins to the drugs is RNA-dependent.
Takeaway
Two drugs, 6AP and GA, can stop the ribosome from helping proteins fold correctly, but they don't stop the ribosome from making proteins.
Methodology
The study used affinity chromatography to identify interactions between the drugs and ribosomal components, assessing their effects on protein folding activity.
Limitations
The study does not explore potential off-target effects of the drugs on other cellular processes.
Digital Object Identifier (DOI)
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