Cited by 509RNA Research and SplicingRNA regulation and diseaseNeuroscience and Neuropharmacology Research

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Nova regulates brain-specific splicing to shape the synapse

Ule, Jernej, Ule, Aljaž, Spencer, Joanna, Williams, Alan, Hu, Jing-Shan, Cline, Melissa, Wang, Hui, Clark, Tyson, Fraser, Claire, Ruggiu, Matteo, Zeeberg, Barry R, Kane, David, Weinstein, John N, Blume, John, Darnell, Robert B·2005·Nature Genetics

DOI 10.1038/ng1610

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Abstract

Alternative RNA splicing greatly increases proteome diversity and may thereby contribute to tissue-specific functions. We carried out genome-wide quantitative analysis of alternative splicing using a custom Affymetrix microarray to assess the role of the neuronal splicing factor Nova in the brain. We used a stringent algorithm to identify 591 exons that were differentially spliced in the brain relative to immune tissues, and 6.6% of these showed major splicing defects in the neocortex of Nova2-/- mice. We tested 49 exons with the largest predicted Nova-dependent splicing changes and validated all 49 by RT-PCR. We analyzed the encoded proteins and found that all those with defined brain functions acted in the synapse (34 of 40, including neurotransmitter receptors, cation channels, adhesion and scaffold proteins) or in axon guidance (8 of 40). Moreover, of the 35 proteins with known interaction partners, 74% (26) interact with each other. Validating a large set of Nova RNA targets has led us to identify a multi-tiered network in which Nova regulates the exon content of RNAs encoding proteins that interact in the synapse.

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Authors: Ule, J., Ule, A., Spencer, J., Williams, A., Hu, J.-S., Cline, M., Wang, H., Clark, T., Fraser, C., Ruggiu, M., Zeeberg, B. R., Kane, D., Weinstein, J. N., Blume, J., & Darnell, R. B.
Affiliations: Howard Hughes Medical Institute (US)
University of Amsterdam (NL)
Affymetrix (United States) (US)
SRA International (United States) (US)
National Institutes of Health (US)
Corresponding author: Darnell, Robert B
ORCID: Ule, Jernej
Ule, Aljaž
Cline, Melissa
Wang, Hui
Clark, Tyson
Ruggiu, Matteo
Kane, David
Weinstein, John N
Blume, John
Darnell, Robert B
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2005-07-24
Volume: 37
Issue: 8
Pages: 844-852
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng1610
OpenAlex: W2118823143
Cited by: 509
References: 49
Citations by year: 2026: 7 · 2025: 16 · 2024: 16 · 2023: 9 · 2022: 12 · 2021: 14 · 2020: 20 · 2019: 13 · 2018: 17 · 2017: 18 · 2016: 19 · 2015: 22 · 2014: 30 · 2013: 25 · 2012: 38
FWCI: 17.19
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: alternative splicing, synapses, neocortex, exon skipping, protein-protein interaction network, axon guidance, neurotransmitter receptors, cation channels, adhesion proteins, scaffold proteins, tissue-specific splicing
MeSH terms: Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Nerve Tissue Proteins, Synapses, RNA-Binding Proteins, Alternative Splicing, Mice, Knockout, Neocortex, Oligonucleotide Array Sequence Analysis, Mice

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Nova regulates brain-specific splicing to shape the synapse

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