"Ribosome Stalling Increases Sup35 Prion Conversion in Saccharomyces ce" by Hayley Kane

Submission Date

2-18-2025

Document Type

Paper- Restricted to Campus Access

Department

Biology

Adviser

Dale Cameron

Committee Member

Rebecca Lyczak

Committee Member

Brent Mattingly

Department Chair

Dale Cameron

Project Description

Proteins are one of the four main macromolecules essential to life. They are responsible for a diverse array of processes, including cellular signaling, cell structure, and catalytic activity. These functions are directly related to the protein’s specific structure. Consequently, the misfolding of a protein, which can be due to a variety of factors, can lead to an alteration in the function of that protein. Misfolded proteins can also associate together to form aggregates, which can become toxic to cells. In prions and prion-like proteins, the misfolding of one protein can propagate to another protein, increasing aggregation, which can lead to cellular death and result in neurodegenerative diseases in mammals. One factor that is linked to increased misfolding is stalling of the ribosome, the cellular machinery responsible for the construction of proteins, during synthesis. In the model organism Saccharomyces cerevisiae, stalling is a natural process that may allow for misfolding to occur in a way that benefits yeast in times of stress. By integrating amino acids sequences known to stall ribosomes into a gene construct including the sequence of the known yeast prion Sup35, the mechanism and frequency at which ribosome stalling influences prion conversion can be investigated. We here demonstrate that ribosome stalling increases the frequency of Sup35 prion conversion when ribosomes are paused using known stalling sequences.

Comments

This research is supported by the National institutes of Health NIGMS Award Number R15GM119081 to DMC.

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