Lin Guo, Jacob R Mann, Jocelyn C Mauna, Katie E Copley, Hejia Wang, Jack D Rubien, Hana M Odeh, JiaBei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin M Kim, Anastasia C Murthy, Tapas Paul, Bede Portz, Amanda M Gleixner, Zamia Diaz, Jenny L Carey, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric J Huang, Alessandra Chesi, Nicolas L Fawzi, Sua Myong, Christopher J Donnelly, James Shorter
RNA-binding proteins with prion-like domains, such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs (24-48 nucleotides) that prevent FUS fibrillization by promoting liquid phases, and distinct short RNAs that prevent and, remarkably, reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure...
September 4, 2023: bioRxiv