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, such as TDP25, are observed in degenerative neuronal cells. However, few reports have focused on small molecules that can reduce their aggregation and cytotoxicity. Here, we show that short RNA repeats of GGGGCC and AAAAUU are molecular chaperones (i.e., chaperone RNAs) that can reduce proteotoxicity by preventing the aggregation of TDP-43 and TDP25. TDP25 interacts with these RNAs, as well as TDP-43, despite the lack of major RNA-recognition motifs, using fluorescence cross-correlation spectroscopy. Expression of these RNAs significantly decreases the cells harboring cytoplasmic aggregates of TDP-43 and TDP25 and ameliorates rounded and shrinking cells by mislocalized TDP-43; furthermore, the cellular transcriptome is not altered. Consequently, these RNAs are molecular chaperones against the aggregation of TDP-43 and TDP25.
Competing Interest Statement
The authors have declared no competing interest.
