RNA Seeds Higher-Order Assembly of FUS Protein

Jacob C. Schwartz; Xueyin Wang; Elaine R. Podell; Thomas R. Cech

doi:10.1016/j.celrep.2013.11.017

RNA Seeds Higher-Order Assembly of FUS Protein

Jacob C. Schwartz, Xueyin Wang, Elaine R. Podell, Thomas R. Cech

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

Abstract

The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II inan 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.

Original language	English (US)
Pages (from-to)	918-925
Number of pages	8
Journal	Cell Reports
Volume	5
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2013.11.017
State	Published - Nov 27 2013
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2013.11.017

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@article{17e138b5d70049678a567f9e636b8f67,

title = "RNA Seeds Higher-Order Assembly of FUS Protein",

abstract = "The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II inan 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.",

author = "Schwartz, {Jacob C.} and Xueyin Wang and Podell, {Elaine R.} and Cech, {Thomas R.}",

note = "Funding Information: We are grateful to S. McKnight (UT Southwestern) for supplying GFP-CTD constructs and stimulating discussions. We thank the following CU Boulder colleagues for their advice on experiments and the manuscript: J. Schmidt, R. Parker, D. Protter, T. Giddings, and A. Erbse. We thank S. Mack for performing initial RNA binding studies as a Howard Hughes Medical Institute EXROP student. J.C.S. is supported by NIGMS NRSA fellowship 1F32GM095311-01. T.R.C. is an investigator of the Howard Hughes Medical Institute. ",

year = "2013",

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doi = "10.1016/j.celrep.2013.11.017",

language = "English (US)",

volume = "5",

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journal = "Cell Reports",

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T1 - RNA Seeds Higher-Order Assembly of FUS Protein

AU - Schwartz, Jacob C.

AU - Wang, Xueyin

AU - Podell, Elaine R.

AU - Cech, Thomas R.

N1 - Funding Information: We are grateful to S. McKnight (UT Southwestern) for supplying GFP-CTD constructs and stimulating discussions. We thank the following CU Boulder colleagues for their advice on experiments and the manuscript: J. Schmidt, R. Parker, D. Protter, T. Giddings, and A. Erbse. We thank S. Mack for performing initial RNA binding studies as a Howard Hughes Medical Institute EXROP student. J.C.S. is supported by NIGMS NRSA fellowship 1F32GM095311-01. T.R.C. is an investigator of the Howard Hughes Medical Institute.

PY - 2013/11/27

Y1 - 2013/11/27

N2 - The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II inan 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.

AB - The abundant nuclear RNA binding protein FUS binds the C-terminal domain (CTD) of RNA polymerase II inan 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.

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JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

RNA Seeds Higher-Order Assembly of FUS Protein

Abstract

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