Prion and anti-codon usage: Does infectious PrP alter tRNA abundance to induce misfolding of PrP?

The "protein-only" hypothesis of prion diseases views the infectious agent as devoid of nucleic acids and consisting of misfolded prion proteins (PrPSc) which, upon infiltration into host cells, act as a template that induces transformation of wild-type protein (PrPC) to the pathological form by unknown mechanisms. The two isoforms are identical in amino-acid composition. By analogy to reported "silent" mutations in which utilization of relatively rare tRNAs alter protein folding pattern, we postulate that misfolded PrPSc alters tRNAs abundance in prion-infected cells and results in different rates of co-translational folding of PrP, leading to the formation of additional misfolded PrPSc. We analyze experiments that might link tRNAs to prions. This concept of "PrP-seed and tRNA-soil" envisages a vicious cycle in which PrPSc levels govern specific tRNA usage, whose alteration subsequently transforms resident PrPC to PrPSc, causing the cycle to repeat itself ad infinitum. (C) 2008 Elsevier Ltd. All rights reserved.