| 研究課題/領域番号 |
18F18384
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| 研究機関 | 国立研究開発法人国立精神・神経医療研究センター |
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研究代表者 |
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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| 研究分担者 |
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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| 研究期間 (年度) |
2018-11-09 – 2021-03-31
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| キーワード | Autophagy / neurodegeneration / RNautophagy / lysosome / SIDT2 |
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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