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

作者：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^*

来源：Neuron, 2017, 94(2): 322-+.

DOI：10.1016/j.neuron.2017.03.026

• LONG NONCODING RNAS
• FRONTOTEMPORAL LOBAR DEGENERATION
• AMYOTROPHIC-LATERAL-SCLEROSIS
• INHERITED DEMENTIA FTDP-17
• AUTISM SPECTRUM DISORDERS
• CENTRAL-NERVOUS-SYSTEM
• INTRON RETENTION
• NEURONAL DEVELOPMENT
• ZEBRAFISH HINDBRAIN
• BIPOLAR DISORDER

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.

• 出版日期2017-4-19
• 单位河北医科大学