Journal article
NOVA2-mediated RNA regulation is required for axonal pathfinding during development
eLife, Vol.5, e14371
05/25/2016
DOI: 10.7554/eLife.14371
PMCID: PMC4930328
PMID: 27223325
Abstract
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.
Details
- Title: Subtitle
- NOVA2-mediated RNA regulation is required for axonal pathfinding during development
- Creators
- Yuhki Saito - Rockefeller UniversitySoledad Miranda-Rottmann - Rockefeller UniversityMatteo Ruggiu - Rockefeller UniversityChristopher Y Park - New York Genome CenterJohn J Fak - Rockefeller UniversityRu Zhong - Rockefeller UniversityJeremy S Duncan - University of IowaBrian A Fabella - Rockefeller UniversityHarald J Junge - University of Colorado BoulderZhe Chen - University of Colorado BoulderRoberto Araya - Université de MontréalBernd Fritzsch - University of IowaA J Hudspeth - Rockefeller UniversityRobert B Darnell - New York Genome Center
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.5, e14371
- DOI
- 10.7554/eLife.14371
- PMID
- 27223325
- PMCID
- PMC4930328
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- England
- Grant note
- R01 NS034389 / NINDS NIH HHS R56 NS034389 / NINDS NIH HHS Howard Hughes Medical Institute R01 NS081706 / NINDS NIH HHS R01 EY024261 / NEI NIH HHS P30 DC010362 / NIDCD NIH HHS
- Language
- English
- Date published
- 05/25/2016
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070511402771
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