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  • NOVA2-mediated RNA regulation is required for axonal pathfinding during development.

NOVA2-mediated RNA regulation is required for axonal pathfinding during development.

eLife (2016-05-26)
Yuhki Saito, Soledad Miranda-Rottmann, Matteo Ruggiu, Christopher Y Park, John J Fak, Ru Zhong, Jeremy S Duncan, Brian A Fabella, Harald J Junge, Zhe Chen, Roberto Araya, Bernd Fritzsch, A J Hudspeth, Robert B Darnell
摘要

The neuron specific RNA-binding proteins NOVA1 and NOVA2 are highly homologous alternative splicing regulators. NOVA proteins regulate at least 700 alternative splicing events in vivo, yet relatively little is known about the biologic consequences of NOVA action and in particular about functional differences between NOVA1 and NOVA2. Transcriptome-wide searches for isoform-specific functions, using NOVA1 and NOVA2 specific HITS-CLIP and RNA-seq data from mouse cortex lacking either NOVA isoform, reveals that NOVA2 uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development. Corresponding axonal pathfinding defects were specific to NOVA2 deficiency: Nova2-/- but not Nova1-/- mice had agenesis of the corpus callosum, and axonal outgrowth defects specific to ventral motoneuron axons and efferent innervation of the cochlea. Thus we have discovered that NOVA2 uniquely regulates alternative splicing of a coordinate set of transcripts encoding key components in cortical, brainstem and spinal axon guidance/outgrowth pathways during neural differentiation, with severe functional consequences in vivo.

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单克隆抗-神经丝蛋白 200 小鼠抗, clone NE14, ascites fluid
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抗-神经细胞粘附分子L1抗体,克隆324, clone 324, Chemicon®, from rat