Related Experiment Video

Updated: Jun 30, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

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

Oded Rechavi1, Yoel Kloog

  • 1Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel-Aviv, Israel. odedrechavi@gmail.com

Medical Hypotheses
|September 24, 2008
PubMed

Insights

Prion diseases may involve misfolded prion proteins (PrPSc) altering transfer RNA (tRNA) abundance. This shift in tRNA levels could influence prion protein folding, creating a self-perpetuating cycle of disease.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Prion diseases are linked to the "protein-only" hypothesis, where misfolded prion proteins (PrPSc) induce normal prion proteins (PrPC) to misfold.
  • The exact mechanism by which PrPSc conversion occurs remains largely unknown, despite identical amino acid sequences between PrPC and PrPSc.

Purpose of the Study:

  • To propose a novel mechanism for prion disease pathogenesis involving transfer RNAs (tRNAs).
  • To explore the potential role of tRNA abundance alterations in the conversion of PrPC to PrPSc.

Main Methods:

  • Analysis of existing experimental data linking tRNAs and prions.
  • Postulation of a "PrP-seed and tRNA-soil" model to explain prion propagation.

Main Results:

  • A hypothesis is presented where misfolded PrPSc influences tRNA abundance within host cells.
  • Altered tRNA levels are suggested to modulate the co-translational folding rates of PrP.
  • This modulation is proposed to lead to the generation of further misfolded PrPSc, perpetuating the disease cycle.

Conclusions:

  • The study introduces a new conceptual framework, the "PrP-seed and tRNA-soil" model, for prion disease.
  • This model suggests a self-sustaining cycle driven by the interplay between PrPSc and cellular tRNA profiles.
  • Further experimental investigation is warranted to validate the role of tRNAs in prion infectivity and propagation.

More Related Videos

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

High-throughput Screening for Protein-based Inheritance in S. cerevisiae08:12

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...