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Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
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Impaired RNA Binding Does Not Prevent Histone Modification Changes in a FUS ALS/FTD Yeast Model
Seth A Bennett1, Samantha N Cobos2, Elizaveta Son3
1PhD. Program in Biochemistry, City University of New York - The Graduate Center, New York, NY, USA 10016.
Micropublication Biology
|September 25, 2023
Summary
FUS protein mutations cause neurodegenerative diseases. Even without binding RNA, FUS protein changes still alter histone modifications linked to these conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Mutations in the RNA-binding protein FUS are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD).
- FUS proteinopathy involves mislocalization and aggregation in neurons.
- Previous studies linked FUS proteinopathy to altered histone modifications in a yeast model.
Purpose of the Study:
- To investigate whether FUS protein's RNA-binding ability is essential for its connection to altered histone modifications in ALS/FTD.
Main Methods:
- Overexpression of a mutant FUS protein lacking RNA-binding capacity in a yeast model.
- Analysis of histone modification levels (H3S10ph, H3K14ac, H3K56ac) in cells expressing the mutant FUS.
Main Results:
- Overexpression of the RNA-binding deficient FUS mutant still led to reduced levels of H3S10ph, H3K14ac, and H3K56ac.
- These findings indicate that FUS's RNA-binding function is not required for the observed changes in histone modifications.
Conclusions:
- FUS protein's ability to bind RNA is not necessary for the mechanism linking FUS proteinopathy to altered histone post-translational modifications.
- This suggests alternative pathways through which FUS proteinopathy impacts epigenetic regulation in ALS/FTD.
