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공공누리This item is licensed Korea Open Government License

Title
Pumilio1 Haploinsufficiency Leads to SCA1-like Neurodegeneration by Increasing Wild-Type Ataxin1 Levels
Author(s)
Vincenzo A. GennarinoHuda Y. ZoghbPaymaan Jafar-NejadAlberto di RonzaJoshua J. WhiteRavi K. SinghThomas A. CooperHarry T. OrrJi-Yoen KimKihoon HanLayal S. SayeghRoy V. Sillitoe강효진
Publication Year
2015-03-12
Abstract
Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative proteinopathy, in which a mutant protein (in this case, ATAXIN1) accumulates in neurons and exerts toxicity; in SCA1, this process causes progressive deterioration of motor coordination. Seeking to understand how post-translational modification of ATAXIN1 levels influences disease, we discovered that the RNA-binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also plays an unexpectedly important role in neuronal function. Loss of Pum1 caused progressive motor dysfunction and SCA1-like neurodegeneration with motor impairment, primarily by increasing Ataxin1 levels. Breeding Pum1+/− mice to SCA1 mice (Atxn1154Q/+) exacerbated disease progression, whereas breeding them to Atxn1+/− mice normalized Ataxin1 levels and largely rescued the Pum1+/− phenotype. Thus, both increased wild-type ATAXIN1 levels and PUM1 haploinsufficiency could contribute to human neurodegeneration. These results demonstrate the importance of studying post-transcriptional regulation of disease-driving proteins to reveal factors underlying neurodegenerative disease.
Keyword
PUM1; SCA1; Neurodegeneration; Ataxin1
Journal Title
Cell
ISSN
0092-8674
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Appears in Collections:
7. KISTI 연구성과 > 학술지 발표논문
URI
https://repository.kisti.re.kr/handle/10580/14376
http://www.ndsl.kr/ndsl/search/detail/article/articleSearchResultDetail.do?cn=NART71648126
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