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 & 1 others Corinne 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 languageEnglish
Pages (from-to)322-336.e5
JournalNeuron
Volume94
Issue number2
DOIs
Publication statusPublished - 19 Apr 2017

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Axons
Zebrafish
Exome
Motor Neurons
Nuclear Proteins
Cell Differentiation
RNA
RNA Splicing Factors

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Thomas-Jinu, S., Gordon, P. M., Fielding, T., Taylor, R., Smith, B. N., Snowden, V., ... 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
Thomas-Jinu, Swapna ; Gordon, Patricia M. ; Fielding, Triona ; Taylor, Richard ; Smith, Bradley N. ; Snowden, Victoria ; Blanc, Eric ; Vance, Caroline ; Topp, Simon ; Wong, Chun Hao ; Bielen, Holger ; Williams, Katherine L. ; McCann, Emily P. ; Nicholson, Garth A. ; Pan-Vazquez, Alejandro ; Fox, Archa H. ; Bond, Charles S. ; Talbot, William S. ; Blair, Ian P. ; Shaw, Christopher E. ; Houart, Corinne. / Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. In: Neuron. 2017 ; Vol. 94, No. 2. pp. 322-336.e5.
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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.",
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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

Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. / Thomas-Jinu, Swapna; Gordon, Patricia M.; Fielding, Triona; Taylor, Richard; Smith, Bradley N.; Snowden, Victoria; Blanc, Eric; Vance, Caroline; Topp, Simon; Wong, Chun Hao; Bielen, Holger; Williams, Katherine L.; McCann, Emily P.; Nicholson, Garth A.; Pan-Vazquez, Alejandro; Fox, Archa H.; Bond, Charles S.; Talbot, William S.; Blair, Ian P.; Shaw, Christopher E.; Houart, Corinne.

In: Neuron, Vol. 94, No. 2, 19.04.2017, p. 322-336.e5.

Research output: Contribution to journalArticle

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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

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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

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SN - 0896-6273

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Thomas-Jinu S, Gordon PM, Fielding T, Taylor R, Smith BN, Snowden V et al. Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. Neuron. 2017 Apr 19;94(2):322-336.e5. https://doi.org/10.1016/j.neuron.2017.03.026