In my understanding, a defect in the RNA that affected the protein would necessarily result in a different amino acid sequence. So for prions to form, they woul

In my understanding, a defect in the RNA that affected the protein would necessarily result in a different amino acid sequence. So for prions to form, they would have to be misfolded initially due to chance / environment or re-arranged afterwards through some process. The best known protein to form prions (PrP, Prion Protein) is known to convert from the well-folded form to a misfolded form upon interacting with the misfolded form, which could indicate that spontaneous formation of prions is due to interaction with something after the initial folding. I think this could also just be an indication that PrP just has lots of very close low-energy states, which would mean a higher chance of misfolding initially. - Mostly lay person view (some bioinformatics experience)