Cellular stress-induced formation of RNA G-quadruplexes accelerates α-Synuclein aggregation
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- Maeda Kohei
- Sch. Pharm., Kumamoto Univ Dept. Geno. Neurol., IMEG., Kumamoto Univ
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- Yabuki Yasushi
- Sch. Pharm., Kumamoto Univ Dept. Geno. Neurol., IMEG., Kumamoto Univ
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- Asamitsu Sefan
- Dept. Geno. Neurol., IMEG., Kumamoto Univ
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- Matsuo Kazuya
- Dept. Geno. Neurol., IMEG., Kumamoto Univ
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- Mizobata Tomohiro
- Dept. Chem. & Biotech., Grad. Sch. Eng., Tottori Univ
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- Kawata Yasushi
- Dept. Chem. & Biotech., Grad. Sch. Eng., Tottori Univ
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- Shioda Norifumi
- Sch. Pharm., Kumamoto Univ Dept. Geno. Neurol., IMEG., Kumamoto Univ
Bibliographic Information
- Other Title
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- 細胞ストレスによるRNAグアニン四重鎖の形成は α-シヌクレインの凝集を促進する
Abstract
<p>Synucleinopathies are neurodegenerative diseases caused by aggregation of α-Synuclein (α-Syn). While it has been suggested that pathogenic α-Syn can spread in the whole brain like a prion protein, those molecular mechanisms are still unknown. Here, we show that RNA G-quadruplexes (G4RNAs) have an important role in α-Syn aggregation. We found that α-Syn binds to guanine-enriched RNA sequences using RNA Bind-n-seq in vitro. In addition, α-Syn preferentially formed a complex with G4RNAs than with other RNA secondary structures. Under the molecular crowding conditions, α-Syn underwent liquid-liquid phase separation (LLPS), and G4RNAs significantly facilitated liquid-to-solid transition of α-Syn. In α-Syn overexpressing cells, α-Syn preformed fibril (PFF) increased G4RNA foci and in turn formed α-Syn aggregates. Furthermore, α-Syn aggregates were colocalized with G4RNA foci in the dopaminergic neurons of α-Syn PFF-injected mice. These observations suggest that G4RNA is a key factor of α-Syn aggregation and cell-to-cell transmission under the pathological condition. We are trying to reveal the mechanisms underlying increases of G4RNA foci by cellular stress, and define endogenous G4RNA forming RNAs involved in α-Syn phase transition.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (0), 1-SS-26-, 2022
Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390291767676148864
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed