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

• DOI: 10.7554/elife.14371
• Publication Date: 2016-05-25T12:01:15Z
• Authors: Yuhki Saito; Soledad Miranda-R...; 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
• Keywords: 572; NOVA; QH301-705.5; Knockout; Science; splicing; Mice; 03 medical and health sciences; Antigens, Neoplasm; Neuro-Oncological Ventral Antigen; Animals; Developmental; Antigens; Biology (General); Cerebral Cortex; Mice, Knockout; Neurons; 0303 health sciences; axon guidance; Q; R; Gene Expression Regulation, Developmental; RNA-Binding Proteins; Axon Guidance; 3. Good health; Gene Expression Regulation; Neoplasm; Medicine; RNA; HITS-CLIP; RNA-seq; agenesis corpus callosum; Neuroscience

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