Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations

Amirhossein Ghanbari Niaki; Jaya Sarkar; Xinyi Cai; Kevin Rhine; Velinda Vidaurre; Brian Guy; Miranda Hurst; Jong Chan Lee; Hye Ran Koh; Lin Guo; Charlotte M. Fare; James Shorter; Sua Myong

doi:10.1016/j.molcel.2019.09.022

Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations

Amirhossein Ghanbari Niaki
, Jaya Sarkar
, Xinyi Cai
, Kevin Rhine
, Velinda Vidaurre
, Brian Guy
, Miranda Hurst
, Jong Chan Lee
, Hye Ran Koh
, Lin Guo
, Charlotte M. Fare
, James Shorter
, Sua Myong

Department of New Biology

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

133 Scopus citations

Abstract

FUS aggregation is pathogenic hallmark of incurable neurodegenerative diseases, including ALS and FTD. Niaki et al. demonstrate that two classes of ALS/FTD-linked mutations display distinct molecular phenotypes. Arginine mutations lead to defective RNA binding, whereas glycine mutations induce quick loss of fluidity, underpinning potentially disparate pathogenic pathways of disease-linked FUS mutants.

Original language	English
Pages (from-to)	82-94.e4
Journal	Molecular Cell
Volume	77
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2019.09.022
State	Published - 2 Jan 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

ALS/FTD
FUS mutation
Karyopherin-β2
RNA interaction
aberrant condensation
dynamic
fluidity
liquid liquid phase separation
single molecule FRET

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10.1016/j.molcel.2019.09.022

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title = "Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations",

abstract = "FUS aggregation is pathogenic hallmark of incurable neurodegenerative diseases, including ALS and FTD. Niaki et al. demonstrate that two classes of ALS/FTD-linked mutations display distinct molecular phenotypes. Arginine mutations lead to defective RNA binding, whereas glycine mutations induce quick loss of fluidity, underpinning potentially disparate pathogenic pathways of disease-linked FUS mutants.",

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doi = "10.1016/j.molcel.2019.09.022",

language = "English",

volume = "77",

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T1 - Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations

AU - Niaki, Amirhossein Ghanbari

AU - Sarkar, Jaya

AU - Cai, Xinyi

AU - Rhine, Kevin

AU - Vidaurre, Velinda

AU - Guy, Brian

AU - Hurst, Miranda

AU - Lee, Jong Chan

AU - Koh, Hye Ran

AU - Guo, Lin

AU - Fare, Charlotte M.

AU - Shorter, James

AU - Myong, Sua

PY - 2020/1/2

Y1 - 2020/1/2

N2 - FUS aggregation is pathogenic hallmark of incurable neurodegenerative diseases, including ALS and FTD. Niaki et al. demonstrate that two classes of ALS/FTD-linked mutations display distinct molecular phenotypes. Arginine mutations lead to defective RNA binding, whereas glycine mutations induce quick loss of fluidity, underpinning potentially disparate pathogenic pathways of disease-linked FUS mutants.

AB - FUS aggregation is pathogenic hallmark of incurable neurodegenerative diseases, including ALS and FTD. Niaki et al. demonstrate that two classes of ALS/FTD-linked mutations display distinct molecular phenotypes. Arginine mutations lead to defective RNA binding, whereas glycine mutations induce quick loss of fluidity, underpinning potentially disparate pathogenic pathways of disease-linked FUS mutants.

KW - ALS/FTD

KW - FUS mutation

KW - Karyopherin-β2

KW - RNA interaction

KW - aberrant condensation

KW - dynamic

KW - fluidity

KW - liquid liquid phase separation

KW - single molecule FRET

UR - https://www.scopus.com/pages/publications/85076918203

U2 - 10.1016/j.molcel.2019.09.022

DO - 10.1016/j.molcel.2019.09.022

M3 - Article

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AN - SCOPUS:85076918203

SN - 1097-2765

VL - 77

SP - 82-94.e4

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -

Loss of Dynamic RNA Interaction and Aberrant Phase Separation Induced by Two Distinct Types of ALS/FTD-Linked FUS Mutations

Abstract

Bibliographical note

Keywords

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