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

Citation data:

Neuron, ISSN: 0896-6273, Vol: 94, Issue: 2, Page: 322-336.e5

Publication Year:
2017
Usage 39
Abstract Views 37
Downloads 2
Social Media 189
Shares, Likes & Comments 176
Tweets 13
Citations 9
Citation Indexes 9
Repository URL:
https://research-repository.uwa.edu.au/en/publications/d6b881bf-bce4-46e0-bdfd-80c68272f8c0; http://research-repository.uwa.edu.au/en/publications/record(d6b881bf-bce4-46e0-bdfd-80c68272f8c0).html
PMID:
28392072
DOI:
10.1016/j.neuron.2017.03.026
PMCID:
PMC5405110
Author(s):
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, Kelly 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 Show More Hide
Publisher(s):
Elsevier BV
Tags:
amyotrophic lateral sclerosis; axonogenesis; central nervous system; motor neurons; neurodegeneration; neurodevelopment; PSF; RNA processing; RNA-binding protein; SFPQ; Neuroscience
Most Recent Tweet View All Tweets
article description
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.