Poster abstracts
Poster number 137 submitted by Chamali Thalagaha Mudiyanselage
Fused in Sarcoma protein recognizes and binds to mRNA methylation
Chamali T. Mudiyanselage (Chemistry and Biochemistry, Kent State University), Sudeshi M. Abedeera (Chemistry and Biochemistry, Kent State University), Aftab Mollah (Chemistry and Biochemistry, Kent State University), Sanjaya Abeysirigunawadena (Chemistry and Biochemistry, Kent State University)
Abstract:
Epitranscriptomics is the post-transcriptional gene expression regulation through RNA modifications and editing. Various RNA modifications, including N1-methyladenosine (m1A), pseudouridine (Ψ), 5-methylcytidine (m5C), and N6-methyladenosine (m6A), which is the most prevalent nucleotide modification in eukaryotic mRNA are observed in epitranscriptomic gene regulation. The m6A modification exerts its influence by recruiting m6A-binding proteins known as m6A readers, such as YTH-domain-containing proteins like YTHDF1-3 and YTHDC1-2. These m6A reader proteins, independently or in conjunction with accessory proteins, play specific roles in various RNA metabolic processes, including mRNA splicing, stabilization, and decay. Reader proteins also influence translation. We have discovered several proteins that bind to methylations, specifically using an RNA pulldown assay. FUS protein was identified as a potential methyl reader that specifically recognizes m6A methylated RNA during these pulldown assays. FUS (Fused in Sarcoma) is a nuclear RNA binding protein, a multidomain protein composed of RRM and ZnF domains known to bind to RNAs. This study identified a sequence close to the ZnF motif that can likely bind to m6A methylations. FUS protein can form membraneless biological condensates with other proteins and nucleic acids under normal cellular conditions. The abnormal aggregation of FUS is linked to several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and essential tremor. Our findings will give insights into the role of m6A methylation in RNA on various diseases related to FUS protein.
References:
Miller LG, Demny M, Tamamis P, Contreras LM. Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain. Comput Struct Biotechnol J. (2023) Jun 30;21:3541-3556.
Deng, H., Gao, K. & Jankovic, J. The role of FUS gene variants in neurodegenerative diseases. Nat Rev Neurol 10, 337–348 (2014).
Jiang, X., Liu, B., Nie, Z. et al. The role of m6A modification in the biological functions and diseases. Sig Transduct Target Ther 6, 74 (2021)
Keywords: FUS, m6A, ALS