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C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent accumulation of Staufen in nucleus

biorxiv. 2019; 
Eun Seon Kim,  Chang Geon Chung,  Yoon Ha Kim,  In Jun Cha, Jeong Hyang Park,  Jaekwang Kim,  Chang Man Ha,  Hyung-Jun Kim,  Sung Bae Lee
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Molecular Biology Reagents V5-PR36, HA-GR36, and Myc-PA36 were subcloned (Genscript, Inc.) into pACU2 vectors (from Chun Han, Cornell University) using BglIII and XhoI sites, and the epitopes were added at the N-terminus. Get A Quote

摘要

Accumulation of RNA in the nucleus is one of the pathological features of C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), yet its potential toxic cellular consequences remain largely undefined. RNA accumulated in the nucleus may interact with and increase nuclear localization of RNA-binding proteins (RBPs). Here, we show in C9-ALS/FTD Drosophila melanogastermodel that Staufen, a double-stranded RBP normally localized in cytoplasm, accumulates in the nucleus, which is in contrast to many nuclear-localized RBPs, such as TDP-43 and FUS, whose cytoplasmic accumulation is thought to be a pathological hallmark of ALS/FTD. We found that in Drosophila neurons expressing ar... More

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