Document Type

Article

Publication Date

Fall 11-27-2013

Publication Title

Cell Reports

Volume

5

Issue

4

First Page

918

Last Page

925

DOI

10.1016/j.celrep.2013.11.017

Abstract

The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNApolymerase 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 ofhigher-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 ofRNA binding proteins.

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