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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)193-195
Number of pages3
JournalMedical Hypotheses
Volume72
Issue number2
DOIs
StatePublished - Feb 2009

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