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Updated: May 27, 2026
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Mating-based Overexpression Library Screening in Yeast
Published on: July 6, 2018
A yeast functional screen predicts new candidate ALS disease genes
Julien Couthouis1, Michael P Hart, James Shorter
1Departments of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Summary
Researchers identified TAF15 as a novel gene linked to amyotrophic lateral sclerosis (ALS). This RNA-binding protein aggregates and causes neurodegeneration, similar to other ALS-associated proteins like TDP-43 and FUS.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease.
- Mutations in RNA-binding proteins TDP-43 and FUS are linked to some ALS cases.
- These proteins contain prion-like domains, suggesting other RNA-binding proteins may also contribute to ALS.
Purpose of the Study:
- To systematically survey RNA-binding proteins for novel ALS-associated candidates.
- To investigate the role of TAF15, a protein with predicted prion-like domains, in ALS pathogenesis.
Main Methods:
- Systematic survey of RNA-binding proteins and bioinformatics prediction of prion-like domains.
- Sequencing of the TAF15 gene in ALS patients and controls.
- In vitro aggregation assays, cell culture experiments, and Drosophila models.
- Immunohistochemistry on postmortem spinal cord tissue.
Main Results:
- Missense variants in TAF15 were identified in ALS patients but not in healthy controls.
- TAF15 variants caused cytoplasmic foci formation in neurons and aggregated in vitro.
- TAF15 induced neurodegeneration in Drosophila, with variants showing increased severity.
- Mislocalization of TAF15 was observed in motor neurons of ALS patients.
Conclusions:
- TAF15 is a novel gene associated with ALS pathogenesis.
- Aggregation-prone RNA-binding proteins may broadly contribute to ALS.
- This study provides a resource for discovering additional ALS genes.
