The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Nova regulates brain-specific splicing to shape the synapse
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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“These data reveal the largest program of neural-regulated AS events defined to date, and that this program is associated with a broader range of functional processes and pathways linked to nervous system biology than previously detected (Boutz et al., 2007; Fagnani et al., 2007; Ule et al., 2005).”
From A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains (2014) · cites this paper as Ule et al., 2005
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Cites
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Self-citationCLIP Identifies Nova-Regulated RNA Networks in the Brain
Ule, J., Jensen, K. B., Ruggiu, M., Mele, A., Ule, A., & Darnell, R. B. (2003) · Science · doi:10.1126/science.1090095 · Cited by 1,120
Self-citationBrown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109
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Research works printed but not linked: 1
- Huang, C.S. et al. Long-term potentiation of slow synaptic inhibition induced by coincidence detection of excitation in the CA1 pyramidal neuron requires Nova-2 function. Cell (in the press).
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Items 501–507 of 507
Michielsen, L., Hsu, J., Joglekar, A., Belchikov, N., Reinders, M. J. T., Tilgner, H., & Mahfouz, A. E. (2026) · Genome biology · doi:10.1186/s13059-026-04015-z · Cited by 3
Regulation of alternative splicing and polyadenylation by genotoxic anti-cancer agents
Tanaka, I. (2019) · theses.fr (ABES) · doi:10.70675/8177333az76a6z4204z808az958753142caf
Grenier, J. M. P. (2021) · theses.fr (ABES) · doi:10.70675/1aab1369zd34cz4476z8c46z39a2c3df85b6
Nova Mediates Experience Dependent Processing of Orb2A mRNA
Gill, J. S. (2013) · Cited by 1
Metadata
- 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
- Venue
- Nature Genetics
- Published
- 2005-07-24
- Volume
- 37
- Issue
- 8
- Pages
- 844-852
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- 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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