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Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development
Swapna Thomas-Jinu1, Patricia M Gordon1, Triona Fielding1
1Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
Neuron
|April 11, 2017
Summary
The splicing factor SFPQ has a non-nuclear role in motor axons, crucial for motor neuron development. Specific variants impairing axonal localization highlight the importance of this domain in motor axon function.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- RNA processing and splicing are complex, with implications for human disorders.
- The splicing factor SFPQ is essential and typically functions in the nucleus.
Purpose of the Study:
- To investigate the role of SFPQ beyond its nuclear function, particularly in motor neuron development.
- To explore the non-nuclear localization and function of SFPQ in motor axons.
Main Methods:
- Utilizing zebrafish (Danio rerio) as a model organism to study motoneuron differentiation and axonal development.
- Analyzing the effects of SFPQ loss-of-function and specific SFPQ variants on motor axon morphology and function.
- Investigating the localization of SFPQ in both nuclear and axonal compartments.
Main Results:
- Complete loss of SFPQ function impairs zebrafish motoneuron differentiation autonomously.
- SFPQ unexpectedly localizes to motor axons, where it plays a crucial role in axonal development and function.
- Cytosolic SFPQ rescues motor axonal defects and restores motility in mutant zebrafish.
- Novel SFPQ variants found in frontotemporal lobar degeneration (fALS) disrupt axonal localization and alter motor axon morphology, confirming the functional requirement of axonal SFPQ.
Conclusions:
- SFPQ possesses a critical non-nuclear, axonal function in motor development.
- The coiled-coil domain of SFPQ is essential for its axonal localization and function.
- These findings reveal a new facet of RNA processing complexity and its link to neurological disorders.