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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
Citations
Cites
Finishing the euchromatic sequence of the human genome
International Human Genome Sequencing Consortium (2004) · Nature · doi:10.1038/nature03001 · Cited by 4,971
From molecular to modular cell biology.
Hartwell, L. H., Hopfield, J. J., Leibler, S., & Murray, A. W. (1999) · Nature · doi:10.1038/35011540 · Cited by 3,632
Light-Directed, Spatially Addressable Parallel Chemical Synthesis
Fodor, S. P. A., Read, J., Pirrung, M. C., Stryer, L., Lu, A. T., & Solas, D. W. (1991) · Science · doi:10.1126/science.1990438 · Cited by 2,697
Transcriptional regulatory code of a eukaryotic genome
Harbison, C. T., Gordon, D. B., Lee, T. I., Rinaldi, N. J., MacIsaac, K. D., Danford, T., Hannett, N. M., Tagne, J., Reynolds, D. B., Yoo, J. Y., et al. (2004) · Nature · doi:10.1038/nature02800 · Cited by 2,135
Metaplasticity: the plasticity of synaptic plasticity
Abraham, W. C., & Bear, M. F. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80018-x · Cited by 1,833
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays
Johnson, J. M., Castle, J. C., Garrett-Engele, P. W., Kan, Z., Loerch, P., Armour, C. D., Santos, R., Schadt, E. E., Stoughton, R. B., & Shoemaker, D. D. (2003) · Science · doi:10.1126/science.1090100 · Cited by 1,418
Hentze, M. W., & Kühn, L. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8175 · Cited by 1,292
GoMiner: a resource for biological interpretation of genomic and proteomic data
Zeebèrg, B. R., Feng, W., Wang, G., Wang, M. D., Fojo, A. T., Sunshine, M., Narasimhan, S., Kane, D. W., Reinhold, W. C., Lababidi, S., et al. (2003) · Genome biology · doi:10.1186/gb-2003-4-4-r28 · Cited by 1,198
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
Self-citationFragile X mental retardation protein targets G quartet mRNAs important for neuronal function
Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., & Darnell, R. B. (2001) · Cell · doi:10.1016/s0092-8674(01)00566-9 · Cited by 952
Self-citationSynCAM, a Synaptic Adhesion Molecule That Drives Synapse Assembly
Biederer, T., Sara, Y., Mozhayeva, M., Atasoy, D., Liu, X., Kavalali, E., & Südhof, T. (2002) · Science · doi:10.1126/science.1072356 · Cited by 834
A Muscleblind Knockout Model for Myotonic Dystrophy
Kanadia, R. N., Johnstone, K. A., Mankodi, A., Lungu, C., Thornton, C. A., Esson, D., Timmers, A. M., Hauswirth, W. W., & Swanson, M. S. (2003) · Science · doi:10.1126/science.1088583 · Cited by 743
Signal Transduction and the Control of Gene Expression
Brivanlou, A. H., & Darnell, J. E. (2002) · Science · doi:10.1126/science.1066355 · Cited by 699
Gerber, A. P., Herschlag, D., & Brown, P. O. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020079 · Cited by 670
Regulation of gene expression and cocaine reward by CREB and ΔFosB
McClung, C. A., & Nestler, E. J. (2003) · Nature Neuroscience · doi:10.1038/nn1143 · Cited by 625
Protein Diversity from Alternative Splicing
Black, D. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00128-8 · Cited by 565
Nova-1 Regulates Neuron-Specific Alternative Splicing and Is Essential for Neuronal Viability
Jensen, K. B., Dredge, B. K., Stefani, G., Zhong, R., Buckanovich, R. J., Okano, H. J., Yang, Y. Y. L., & Darnell, R. B. (2000) · Neuron · doi:10.1016/s0896-6273(00)80900-9 · Cited by 426
Self-citationGenomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays
Clark, T. A., Sugnet, C. W., & Ares, M. (2002) · Science · doi:10.1126/science.1069415 · Cited by 411
Self-citationIdentifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays
Tenenbaum, S. A., Carson, C. C., Lager, P. J., & Keene, J. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14085 · Cited by 407
Xu, X., Yang, D., Ding, J.-H., Wang, W., Chu, P., Dalton, N. D., Wang, H., Bermingham, J. R., Ye, Z., Liu, F. C., et al. (2005) · Cell · doi:10.1016/j.cell.2004.11.036 · Cited by 391
Self-citationAngo, F., Cristo, G. D., Higashiyama, H., Bennett, V., Wu, P., & Huang, Z. J. (2004) · Cell · doi:10.1016/j.cell.2004.10.004 · Cited by 358
Regulation of repulsion versus adhesion by different splice forms of an Eph receptor
Holmberg, J., Clarke, D. L., & Frisén, J. (2000) · Nature · doi:10.1038/35041577 · Cited by 335
Sequence-Specific RNA Binding by a Nova KH Domain
Lewis, H. A., Musunuru, K., Jensen, K. B., Edo, C., Chen, H., Darnell, R. B., & Burley, S. K. (2000) · Cell · doi:10.1016/s0092-8674(00)80668-6 · Cited by 326
Self-citationPan, Q., Shai, O., Misquitta, C., Zhang, W., Saltzman, A. L., Mohammad, N., Babak, T., Siu, H., Hughes, T. R., Morris, Q. D., et al. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.12.004 · Cited by 323
The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster
Nagoshi, R. N., McKeown, M., Burtis, K. C., Belote, J. M., & Baker, B. S. (1988) · Cell · doi:10.1016/0092-8674(88)90384-4 · Cited by 280
Zeebèrg, B. R., Qin, H., Narasimhan, S., Sunshine, M., Cao, H., Kane, D. W., Reimers, M., Stephens, R. M., Bryant, D., Burt, S. K., et al. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-168 · Cited by 279
Self-citationCell signalling and the control of pre-mRNA splicing
Shin, C., & Manley, J. L. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1467 · Cited by 278
Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx
Livesey, F. J., Furukawa, T., Steffen, M. A., Church, G. M., & Cepko, C. L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00379-1 · Cited by 272
Burgess, R., Nguyen, Q., Son, Y., Lichtman, J., & Sanes, J. (1999) · Neuron · doi:10.1016/s0896-6273(00)80751-5 · Cited by 257
Hedley, M. L., & Maniatis, T. (1991) · Cell · doi:10.1016/0092-8674(91)90090-l · Cited by 247
Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization
Kobrinsky, E., Mirshahi, T., Zhang, H., Jin, T., & Logothetis, D. E. (2000) · Nature Cell Biology · doi:10.1038/35019544 · Cited by 228
Yang, Y. Y. L., Yin, G. L., & Darnell, R. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13254 · Cited by 219
Self-citationThe neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro and in vivo
Buckanovich, R. J., & Darnell, R. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3194 · Cited by 217
Self-citationHieronymus, H., & Silver, P. A. (2003) · Nature Genetics · doi:10.1038/ng1080 · Cited by 197
Buckanovich, R., Yang, Y., & Darnell, R. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-03-01114.1996 · Cited by 192
Self-citationNova autoregulation reveals dual functions in neuronal splicing
Dredge, B. K., Stefani, G., Engelhard, C. C., & Darnell, R. B. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600630 · Cited by 125
Self-citationDredge, B. K., & Darnell, R. B. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.13.4687-4700.2003 · Cited by 120
Self-citationRegulation of the Ca2+/CaM-Responsive Pool of CaMKII by Scaffold-Dependent Autophosphorylation
Lu, C. S., Hodge, J. J. L., Mehren, J. E., Sun, X. X., & Griffith, L. C. (2003) · Neuron · doi:10.1016/s0896-6273(03)00786-4 · Cited by 100
Le, K., Mitsouras, K., Roy, M., Wang, Q., Xu, Q., Nelson, S. F., & Lee, C. J. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh173 · Cited by 100
Gene structure-based splice variant deconvolution using a microarry platform
Wang, H., Hubbell, E. A., Hu, J., Mei, G., Cline, M., Lu, G., Clark, T. A., Siani-Rose, M. A., Ares, M., Kulp, D., et al. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg1044 · Cited by 100
Self-citationGao, W., Shinsky, N., Armanini, M. P., Moran, P., Zheng, J. L., Mendoza-Ramírez, J.-L., PHILLIPS, H. S., Winslow, J. W., & Caras, I. W. (1998) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1998.0696 · Cited by 74
Specific SR protein-dependent splicing substrates identified through genomic SELEX
Kim, S. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg286 · Cited by 69
Identification of mRNAs Associated with αCP2-Containing RNP Complexes
Waggoner, S. A., & Liebhaber, S. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.19.7055-7067.2003 · Cited by 68
Defining of the Minimal Domain of Protein 4.1 Involved in Spectrin-Actin Binding
Schischmanoff, P. O., Winardi, R., Discher, D. E., Parra, M., Bicknese, S. E., Witkowska, H. E., Conboy, J. G., & Mohandas, N. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.21243 · Cited by 59
Dateki, M., Horii, T., Kasuya, Y., Mochizuki, R., Nagao, Y., Ishida, J., Sugiyama, F., Tanimoto, K., Yagami, K., Imai, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414033200 · Cited by 53
Parra, M., Gee, S. L., Chan, N., Ryaboy, D. V., Dubchak, I. L., Mohandas, N., Gascard, P. D., & Conboy, J. G. (2004) · Genomics · doi:10.1016/j.ygeno.2004.06.004 · Cited by 35
Balla, Z., Hoch, B., Karczewski, P., & Blasig, I. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200553200 · Cited by 17
Wheeler, R. M. (2002) · Lecture notes in computer science · doi:10.1007/3-540-45784-4_15 · Cited by 9
Flagged first, then by citations
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).
Cited by
Sorted by citations
HITS-CLIP yields genome-wide insights into brain alternative RNA processing
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“For example, YCAY-rich HITS-CLIP clusters were present downstream of the known Nova2 target Grin1 exon 19 (E19; Fig 1b-c(ii))20, in a position previously predicted by the Nova bioinformatic map18 (Supplemental Fig.”
Self-citationMechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284
MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery
Wang, K., Singh, D., Zeng, Z., Coleman, S. J., Huang, Y., Savich, G. L., He, X., Mieczkowski, P., Grimm, S. A., Perou, C. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq622 · Cited by 1,193
iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
König, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D. J., Luscombe, N. M., & Ule, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1838 · Cited by 1,126
Self-citationThe SR protein family of splicing factors: master regulators of gene expression
Long, J. C., & Cáceres, J. F. (2008) · Biochemical Journal · doi:10.1042/bj20081501 · Cited by 1,125
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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