Genome-wide translational changes induced by the prion [PSI+]

Area of Science:

• Molecular Biology
• Protein Folding and Propagation
• Genetics and Genomics

Background:

• Prions are infectious proteins known for conformational templating.
• [PSI(+)] is a prion form of the yeast protein eRF3, influencing cellular phenotypes.
• The specific genes regulated by [PSI(+)] have not been previously identified.

Purpose of the Study:

• To identify genes and regulatory mechanisms affected by the [PSI(+)] prion.
• To understand how [PSI(+)] influences gene expression and cellular function.
• To investigate the broader impact of [PSI(+)] on protein synthesis.

Main Methods:

• Ribosome profiling was employed to compare isogenic [PSI(+)] and [psi(-)] yeast strains.
• Analysis focused on identifying changes in gene expression and translation events.
• Investigated stop codon readthrough and reading frame selection.

Main Results:

• Over 100 genes exhibited stop codon readthrough events in the presence of [PSI(+)].
• Expression of many stress-response genes was found to be repressed by [PSI(+)].
• [PSI(+)] was observed to influence reading frame selection independently of termination efficiency.

Conclusions:

• The [PSI(+)] prion has a more extensive regulatory role than previously understood.
• These findings provide molecular explanations for phenotypic variations between [PSI(+)] and [psi(-)] strains.
• [PSI(+)] affects multiple levels of gene expression, including termination and frame selection.