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Related Experiment Video

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Isolation and Quantification of Axonal mRNAs Using Porous Membrane Inserts and RTddPCR
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NOVA2-mediated RNA regulation is required for axonal pathfinding during development.

Yuhki Saito1, Soledad Miranda-Rottmann1, Matteo Ruggiu1

  • 1Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.

Elife
|May 26, 2016
PubMed
Summary
This summary is machine-generated.

The neuron-specific RNA-binding proteins NOVA1 and NOVA2 regulate gene splicing. NOVA2 uniquely controls splicing of axon guidance genes, leading to specific brain and spinal cord defects in mice lacking NOVA2.

Keywords:
HITS-CLIPNOVARNA-seqagenesis corpus callosumaxon guidancecochlear neuronmotoneuronmouseneurosciencesplicing

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Neuron-specific RNA-binding proteins NOVA1 and NOVA2 are homologous regulators of alternative splicing.
  • NOVA proteins influence over 700 alternative splicing events, but their distinct biological roles remain unclear.

Purpose of the Study:

  • To investigate the isoform-specific functions of NOVA1 and NOVA2.
  • To identify the biological consequences of differential NOVA1 and NOVA2 activity in neural development.

Main Methods:

  • Utilized HITS-CLIP and RNA-seq on mouse cortex lacking either NOVA1 or NOVA2.
  • Performed transcriptome-wide analysis to identify isoform-specific splicing events and their downstream effects.

Main Results:

  • NOVA2 uniquely regulates alternative splicing of multiple axon guidance genes during cortical development.
  • Mice deficient in NOVA2 (Nova2-/-), but not NOVA1 (Nova1-/-), exhibited agenesis of the corpus callosum.
  • NOVA2 deficiency caused specific axonal pathfinding defects in ventral motoneurons and cochlear efferent innervation.

Conclusions:

  • NOVA2 plays a unique and critical role in regulating alternative splicing of transcripts involved in cortical, brainstem, and spinal axon guidance pathways.
  • Differential regulation by NOVA2 has significant in vivo functional consequences for neural differentiation and development.