Short repeat RNA reduces cytotoxicity by preventing the aggregation of TDP-43 and its 25 kDa carboxy-terminal fragment

• DOI: 10.1101/2022.07.03.498631
• Publication Date: 2022-07-06T19:20:13Z
• Authors: Ai Fujimoto; Masataka Kinjo; Akira Kitamura
• Keywords: Proteostasis

Abstract TAR DNA/RNA-binding protein 43 kDa (TDP-43) proteinopathy is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis, in which cytoplasmic aggregates containing TDP-43 and its C-terminal fragments, TDP25, are observed degenerative neuronal cells. However, few reports have focused on small molecules that can reduce their aggregation cytotoxicity. Here, we show short RNA repeats GGGGCC AAAAUU aggregation-suppressors TDP25. TDP25 interacts with these RNAs, well TDP-43, despite the lack major RNA-recognition motifs, using fluorescence cross-correlation spectroscopy. Expression RNAs significantly decreases cells harboring ameliorates rounded shrinking by mislocalized TDP-43; furthermore, cellular transcriptome not altered. Consequently, maintain proteostasis preventing