RRC ID 51269
Author 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.
Title Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development.
Journal Neuron
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.
Volume 94(2)
Pages 322-336.e5
Published 2017-4-19
DOI 10.1016/j.neuron.2017.03.026
PII S0896-6273(17)30238-6
PMID 28392072
PMC PMC5405110
MeSH Amyotrophic Lateral Sclerosis / metabolism Animals Axons / metabolism* DNA-Binding Proteins / metabolism Humans Mice Motor Cortex / growth & development Motor Neurons / metabolism* PTB-Associated Splicing Factor / genetics PTB-Associated Splicing Factor / metabolism* RNA Splicing / genetics* RNA, Messenger / metabolism RNA-Binding Proteins / metabolism Zebrafish
IF 14.415
Times Cited 20
Zebrafish Tg(CM-isl1:GFP)