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Cell Rep. 2013 Nov 27;5(4):918-25. doi: 10.1016/j.celrep.2013.11.017. Epub 2013 Nov 21.

RNA seeds higher-order assembly of FUS protein.

Author information

1
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
2
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: thomas.cech@colorado.edu.

Abstract

The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II in an RNA-dependent manner, affecting Ser2 phosphorylation and transcription. Here, we examine the mechanism of this process and find that RNA binding nucleates the formation of higher-order FUS ribonucleoprotein assemblies that bind the CTD. Both the low-complexity domain and the arginine-glycine rich domain of FUS contribute to assembly. The assemblies appear fibrous by electron microscopy and have characteristics of β zipper structures. These results support the emerging view that the pathologic protein aggregation seen in neurodegenerative diseases such as amyotrophic lateral sclerosis may occur via the exaggeration of functionally important assemblies of RNA binding proteins.

PMID:
24268778
PMCID:
PMC3925748
DOI:
10.1016/j.celrep.2013.11.017
[Indexed for MEDLINE]
Free PMC Article

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