ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP

DSpace/Manakin Repository

ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP

Citable link to this page

 

 
Title: ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP
Author: Sun, Shuying; Ling, Shuo-Chien; Qiu, Jinsong; Albuquerque, Claudio P.; Zhou, Yu; Tokunaga, Seiya; Li, Hairi; Qiu, Haiyan; Bui, Anh; Yeo, Gene W.; Huang, Eric J.; Eggan, Kevin; Zhou, Huilin; Fu, Xiang-Dong; Lagier-Tourenne, Clotilde; Cleveland, Don W.

Note: Order does not necessarily reflect citation order of authors.

Citation: Sun, S., S. Ling, J. Qiu, C. P. Albuquerque, Y. Zhou, S. Tokunaga, H. Li, et al. 2015. “ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP.” Nature communications 6 (1): 6171. doi:10.1038/ncomms7171. http://dx.doi.org/10.1038/ncomms7171.
Full Text & Related Files:
Abstract: The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease ALS, is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and dysregulate its function, including loss of Gems and altered levels of small nuclear RNAs (snRNAs). The same mutants are found to have reduced association with U1-snRNP. Correspondingly, global RNA analysis reveals a mutant-dependent loss of splicing activity, with ALS-linked mutants failing to reverse changes caused by loss of wild-type FUS/TLS. Furthermore, a common FUS/TLS mutant-associated RNA splicing signature is identified in ALS patient fibroblasts. Taken together, these studies establish potentially converging disease mechanisms in ALS and spinal muscular atrophy, with ALS-causative mutants acquiring properties representing both gain (dysregulation of SMN) and loss (reduced RNA processing mediated by U1-snRNP) of function.
Published Version: doi:10.1038/ncomms7171
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338613/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820644
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters