Can I read Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model on EtoBox?

Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model by Shibata, Tomonori (author);Nagano, Konami (author);Ueyama, Morio (author);Ninomiya, Kensuke (author);Hirose, Tetsuro (author);Nagai, Yoshitaka (author);Ishikawa, Kinya (author);Kawai, Gota (author);Nakatani, Kazuhiko (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model about?

## Abstract Synthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here we report our discovery that naphthyridine carbamate dimer (NCD) targets disease-causing r(UGGAA)~n~ repeat RNAs in spinocerebellar ataxia type 31 (SCA31). Structural analysis of the NCD-UGGAA/UGGAA complex by nuclear magnetic resonance (NMR) spectroscopy clarifies the mode of binding that recognizes four guanines in the UGGAA/UGGAA pentad by hydrogen bonding with four naphthyridine moieties of two NCD molecules. Biological studies show that NCD disrupts naturally occurring RNA foci built on r(UGGAA)~n~ repeat RNA known as nuclear stress bodies (nSBs) by interfering with RNA–protein interactions resulting in the suppression of nSB-mediated splicing events. Feeding NCD to larvae of the Drosophila model of SCA31 alleviates the disease phenotype induced by toxic r(UGGAA)~n~ repeat RNA. These studies demonstrate that small molecules targeting toxic repeat RNAs are a promising chemical tool for studies on repeat expansion diseases.

Who reads Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model?

Author

Shibata, Tomonori (author);Nagano, Konami (author);Ueyama, Morio (author);Ninomiya, Kensuke (author);Hirose, Tetsuro (author);Nagai, Yoshitaka (author);Ishikawa, Kinya (author);Kawai, Gota (author);Nakatani, Kazuhiko (author)

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)