Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development

Swapna Thomas-Jinu; Patricia M. Gordon; Triona Fielding; Richard Taylor; Bradley N. Smith; Victoria Snowden; Eric Blanc; Caroline Vance; Simon Topp; Chun Hao Wong; Holger Bielen; Katherine L. Williams; Emily P. McCann; Garth A. Nicholson; Alejandro Pan-Vazquez; Archa H. Fox; Charles S. Bond; William S. Talbot; Ian P. Blair; Christopher E. Shaw; Corinne Houart

doi:10.1016/j.neuron.2017.03.026

Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development

Swapna Thomas-Jinu, Patricia M. Gordon, Triona Fielding, Richard Taylor, Bradley N. Smith, Victoria Snowden, Eric Blanc, Caroline Vance, Simon Topp, Chun Hao Wong, Holger Bielen, Katherine L. Williams, Emily P. McCann, Garth A. Nicholson, Alejandro Pan-Vazquez, Archa H. Fox, Charles S. Bond, William S. Talbot, Ian P. Blair, Christopher E. ShawCorinne Houart

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Abstract

Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. Video Abstract.

Original language	English
Pages (from-to)	322-336.e5
Journal	Neuron
Volume	94
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2017.03.026
Publication status	Published - 19 Apr 2017

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10.1016/j.neuron.2017.03.026

Thomas-Jinu et al., 2018 Non-nuclear pool of splicing
@2017 The Author(s). Published by Elsevier Inc.This is an open access article under the CC BY license http://creativecommons.org/licenses/by/4.0/).
Final published version, 6.69 MBLicence: CC BY

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Thomas-Jinu, S., Gordon, P. M., Fielding, T., Taylor, R., Smith, B. N., Snowden, V., Blanc, E., Vance, C., Topp, S., Wong, C. H., Bielen, H., Williams, K. L., McCann, E. P., Nicholson, G. A., Pan-Vazquez, A., Fox, A. H., Bond, C. S., Talbot, W. S., Blair, I. P., ... Houart, C. (2017). Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. Neuron, 94(2), 322-336.e5. https://doi.org/10.1016/j.neuron.2017.03.026

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title = "Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development",

abstract = "Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. Video Abstract.",

keywords = "amyotrophic lateral sclerosis, axonogenesis, central nervous system, motor neurons, neurodegeneration, neurodevelopment, PSF, RNA processing, RNA-binding protein, SFPQ",

author = "Swapna Thomas-Jinu and Gordon, {Patricia M.} and Triona Fielding and Richard Taylor and Smith, {Bradley N.} and Victoria Snowden and Eric Blanc and Caroline Vance and Simon Topp and Wong, {Chun Hao} and Holger Bielen and Williams, {Katherine L.} and McCann, {Emily P.} and Nicholson, {Garth A.} and Alejandro Pan-Vazquez and Fox, {Archa H.} and Bond, {Charles S.} and Talbot, {William S.} and Blair, {Ian P.} and Shaw, {Christopher E.} and Corinne Houart",

year = "2017",

month = apr,

day = "19",

doi = "10.1016/j.neuron.2017.03.026",

language = "English",

volume = "94",

pages = "322--336.e5",

journal = "Neuron",

issn = "0896-6273",

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Thomas-Jinu, S, Gordon, PM, Fielding, T, Taylor, R, Smith, BN, Snowden, V, Blanc, E, Vance, C, Topp, S, Wong, CH, Bielen, H, Williams, KL, McCann, EP, Nicholson, GA, Pan-Vazquez, A, Fox, AH , Bond, CS, Talbot, WS, Blair, IP, Shaw, CE & Houart, C 2017, 'Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development', Neuron, vol. 94, no. 2, pp. 322-336.e5. https://doi.org/10.1016/j.neuron.2017.03.026

TY - JOUR

T1 - Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development

AU - Thomas-Jinu, Swapna

AU - Gordon, Patricia M.

AU - Fielding, Triona

AU - Taylor, Richard

AU - Smith, Bradley N.

AU - Snowden, Victoria

AU - Blanc, Eric

AU - Vance, Caroline

AU - Topp, Simon

AU - Wong, Chun Hao

AU - Bielen, Holger

AU - Williams, Katherine L.

AU - McCann, Emily P.

AU - Nicholson, Garth A.

AU - Pan-Vazquez, Alejandro

AU - Fox, Archa H.

AU - Bond, Charles S.

AU - Talbot, William S.

AU - Blair, Ian P.

AU - Shaw, Christopher E.

AU - Houart, Corinne

PY - 2017/4/19

Y1 - 2017/4/19

N2 - Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. Video Abstract.

AB - Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. Video Abstract.

KW - amyotrophic lateral sclerosis

KW - axonogenesis

KW - central nervous system

KW - motor neurons

KW - neurodegeneration

KW - neurodevelopment

KW - PSF

KW - RNA processing

KW - RNA-binding protein

KW - SFPQ

UR - http://www.scopus.com/inward/record.url?scp=85017187298&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2017.03.026

DO - 10.1016/j.neuron.2017.03.026

M3 - Article

C2 - 28392072

AN - SCOPUS:85017187298

SN - 0896-6273

VL - 94

SP - 322-336.e5

JO - Neuron

JF - Neuron

IS - 2

ER -

Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development

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Erratum: Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development (Neuron (2017) 94(2) (322–336.e5)(S0896627317302386)(10.1016/j.neuron.2017.03.026))

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