2018 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 | lysosomal degradation / RNautophagy / lysosome |
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| Outline of Annual Research Achievements |
RNautophagy/DNautophagy (RDA) is a novel RNA/DNA degradation process performed by lysosomes, during which RNA/DNA is directly imported into lysosomes in the presence of ATP and then degraded. RNautophagy was found to degrade RNA linked to the pathology of neurodegenerative diseases such as amyotrophic lateral sclerosis. 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. New insights into the molecular machinery that intermediates the direct uptake of nucleic acids by lysosomes are being provided. The fellow elucidated whether nucleic acids are taken up by lysosomes through a transporter or through microautophagy during RDA.
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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 elucidated whether nucleic acids are taken up by lysosomes through a transporter or through microautophagy during RDA.
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| Strategy for Future Research Activity |
The fellow intends to elucidate whether SIDT2 is a channel protein and whether oligonucleotides can pass through the pore formed by SIDT2. An electrophysiological method, the droplet contact method, and electron microscopy will mainly be used.
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