Poster abstracts
Poster number 95 submitted by Chamali Thalagaha Mudiyanselage
Investigation of the impact of m6A nucleotide modification on FUS-dependent biological liquid-liquid phase separation
Chamali T. Mudiyanselage (Department of Chemistry and Biochemistry, Kent State University), Sudeshi M. Abedeera (Department of Chemistry and Biochemistry, Kent State University), Sanjaya Abeysirigunawardena (Department of Chemistry and Biochemistry, Kent State University)
Abstract:
DNA encodes genetic information that is transcribed into RNA, which not only mediates protein synthesis but also regulates gene expression. The most common internal RNA modification in eukaryotes, N6 methyladenosine (m6A), influences RNA splicing, export, stability, and translation. This reversible modification enables rapid cellular responses to environmental changes. m6A regulation involves three main groups of proteins: “writers” that add the methyl group, “erasers” that remove it, and “readers” that interpret its function. FUS (Fused in Sarcoma) protein was among the proteins enriched in RNA pulldown assay performed using an m6A-modified RNA, suggesting the ability of FUS to function as a potential methyl reader protein. FUS is a 526-amino acid RNA-binding protein involved in transcription, splicing, and RNA transport. It contains several motifs, such as RNA recognition motif and zinc finger motif, that bind to various RNAs and help regulate gene expression and maintain RNA homeostasis. FUS is reported to form liquid–liquid phase separation (LLPS) due to the ability of its N-terminal prion-like domain to form protein-protein interactions. Dysregulation of this process is linked to neurodegenerative diseases such as ALS. In this study, we show that m6A nucleotide modification influences the dynamics of FUS-mediated LLPS. These observations will provide valuable insights into potential therapeutic targets for neurodegenerative diseases in the future.
References:
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Keywords: FUS, LLPS, m6A modifications