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CLIP Identifies Nova-Regulated RNA Networks in the Brain
Abstract
Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition.Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA.To identify Nova RNA targets, we developed a method to purify protein-RNA complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation (CLIP).Thirty-four transcripts were identified multiple times by Nova CLIP.Three-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibition.Splicing targets confirmed in Nova –/– mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory γ-aminobutyric acid and glycine receptors, two previously identified Nova splicing targets.Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA.
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“Many NOVA2 target genes, including the GABAB receptor 2 (Gabbr2), glycine receptor α2 (Glra2), gephyrin (Gphn) and the inward rectifier potassium channel Kir3.2 (Girk2), are involved in inhibitory synapse function99”
From The neurogenetics of alternative splicing (2016) · cites this paper as [99]
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Metadata
- Authors
- Ule, J., Jensen, K. B., Ruggiu, M., Mele, A., Ule, A., & Darnell, R. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.
- Corresponding author
- Ule, Jernej
- Jensen, Kirk B.
- Darnell, Robert B.
- Venue
- Science
- Published
- 2003-11-14
- Volume
- 302
- Issue
- 5648
- Pages
- 1212-1215
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2053998703
- Cited by
- 1,120
- References
- 32
- Citations by year
- 2026: 36 · 2025: 49 · 2024: 37 · 2023: 32 · 2022: 46 · 2021: 60 · 2020: 49 · 2019: 74 · 2018: 63 · 2017: 68 · 2016: 56 · 2015: 70 · 2014: 72 · 2013: 62 · 2012: 60
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health (5k01mh064753-02)
- National Institute of Mental Health (K01 MH64753)
- National Institute of Neurological Disorders and Stroke (R01NS040955, R01 NS34389, R01NS034389, NS40955)
- 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
- RNA splicing regulation, CLIP, inhibitory synapses, GABA receptors, glycine receptor, gephyrin, neogenin, motor inhibition
- MeSH terms
- Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Brain, Carrier Proteins, Exons, Introns, Membrane Proteins, Nerve Tissue Proteins, Neural Inhibition, Neurons, Precipitin Tests, RNA Precursors, RNA, Messenger, Ultraviolet Rays, RNA-Binding Proteins, Alternative Splicing, Reverse Transcriptase Polymerase Chain Reaction, 3' Untranslated Regions, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 9, Mice
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