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C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons
- Title
- C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons
- Authors
- Kim, Eun Seon; Chung, Chang Geon; Park, Jeong Hyang; Ko, Byung Su; Park, Sung Soon; Kim, Yoon Ha; Cha, In Jun; Kim, Jae kwang; Ha, Chang Man; Kim, Hyung Jun; Lee, Sung Bae
- DGIST Authors
- Kim, Eun Seon; Chung, Chang Geon; Park, Jeong Hyang; Ko, Byung Su; Park, Sung Soon; Kim, Yoon Ha; Cha, In Jun; Kim, Jae kwang; Ha, Chang Man; Kim, Hyung Jun; Lee, Sung Bae
- Issue Date
- 2021-06
- Citation
- Human Molecular Genetics, 30(12), 1084-1100
- Type
- Article
- Keywords
- DOUBLE-STRANDED-RNAHEXANUCLEOTIDE REPEATBINDING PROTEINSRIBOSOMAL-RNANUCLEOCYTOPLASMIC TRANSPORTC9ORF72EXPANSIONLOCALIZATIONTRANSLATIONNUCLEOLUS
- ISSN
- 0964-6906
- Abstract
- RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP Staufen may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS-but not with mutated endogenous NLS-potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/-), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/- is protective. stau+/- also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD. © The Author(s) 2021. Published by Oxford University Press.
- URI
- http://hdl.handle.net/20.500.11750/15381
- DOI
- 10.1093/hmg/ddab089
- Publisher
- Oxford University Press
- Related Researcher
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Lee, Sung Bae
Laboratory of Neurodegenerative Diseases and Aging
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Research Interests
Cellular mechanism of neurodegenerative diseases; Neuronal maintenance and remodeling; 퇴행성 뇌질환의 세포기전; 신경계 유지 및 리모델링 연구
- Files:
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- Collection:
- Department of Brain SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles
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