Impaired RNA Binding Does Not Prevent Histone Modification Changes in a FUS ALS/FTD Yeast Model

Seth A Bennett; Samantha N Cobos; Elizaveta Son; Rianna Segal; Shana Mathew; Huda Yousuf; Mariana P Torrente

doi:10.17912/micropub.biology.000895

Impaired RNA Binding Does Not Prevent Histone Modification Changes in a FUS ALS/FTD Yeast Model

MicroPubl Biol. 2023 Sep 8:2023:10.17912/micropub.biology.000895. doi: 10.17912/micropub.biology.000895. eCollection 2023.

Authors

Seth A Bennett^#¹, Samantha N Cobos^#², Elizaveta Son³, Rianna Segal³, Shana Mathew³, Huda Yousuf³, Mariana P Torrente^{3

4}

Affiliations

¹ PhD. Program in Biochemistry, City University of New York - The Graduate Center, New York, NY, USA 10016.
² PhD. Program in Chemistry, City University of New York - The Graduate Center, New York, NY, USA 10016.
³ Department of Chemistry and Biochemistry, Brooklyn College, Brooklyn, NY, USA 11210.
⁴ PhD. Programs in Chemistry, Biochemistry, and Biology, City University of New York - The Graduate Center, New York, NY, USA 10016.

^# Contributed equally.

Abstract

Mutations in the RNA-binding protein FUS are linked to amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). FUS mutants mislocalize and aggregate in dying neurons. We previously established that FUS proteinopathy is linked to changes in the histone modification landscape in a yeast ALS/FTD model. Here, we examine whether FUS' RNA binding is necessary for this connection. We find that overexpression of a FUS mutant unable to bind RNA is still associated with reduced levels of H3S10ph, H3K14ac and H3K56ac. Hence, FUS' ability to bind RNA is not required in the mechanism connecting FUS proteinopathy to altered histone post-translational modifications.

Grants and funding

R15 NS125394/NS/NINDS NIH HHS/United States