2019 Fiscal Year Annual Research Report
核酸を分解する膜透過型オートファジーのメカニズムと疾患との関連
| Project/Area Number |
18F18384
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
株田 智弘 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 室長 (70535765)
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| Co-Investigator(Kenkyū-buntansha) |
CONTU VIORICA 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 外国人特別研究員
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| Project Period (FY) |
2018-11-09 – 2021-03-31
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| Keywords | Autophagy / neurodegeneration / RNautophagy / lysosome / SIDT2 |
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| Outline of Annual Research Achievements |
RNautophagy/DNautophagy (RDA) is a novel degradation pathway in lysosomes, where RNA/DNA is directly imported into lysosomes in the presence of ATP and then degraded. RNautophagy was found to degrade RNA associated with neurodegenerative conditions. In addition, we have reported that RNautophagy is an important pathway for intracellular RNA degradation and that SIDT2 mediates the translocation of RNA/DNA across the lysosomal membrane during RDA. Through this study, the fellow aims to characterize the molecular machinery of RDA and investigate the physiological significance and possible implications of RNautophagy in neurodegeneration. The results point out the importance of nucleic acid-binding capacity of SIDT2 for its function in translocating nucleic acids through the lipid bilayer and suggest a potential application of RNautophagy activation to reduce the expression levels of disease-causing toxic proteins.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Experiments are on schedule. New insights into the molecular machinery that intermediates the direct uptake of nucleic acids by lysosomes are being provided. The fellow reported about the importance of RNA binding capacity of SIDT2 for its function during RNautophagy and about a potential application of RNautophagy activation to reduce the expression levels of disease-causing toxic proteins.
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| Strategy for Future Research Activity |
The fellow is expected to clarify whether SIDT2 is a channel protein and whether RNA and DNA can pass through the pore formed by SIDT2. Proteoliposomes containing SIDT2 will mainly be used as experimental material. An electrophysiological method, the droplet contact method, and electron microscopy will mainly be applied for data collection.
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