Cited by 1,120RNA Research and SplicingRNA regulation and diseaseNeuroscience and Neuropharmacology Research

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CLIP Identifies Nova-Regulated RNA Networks in the Brain

Ule, Jernej, Jensen, Kirk B., Ruggiu, Matteo, Mele, Aldo, Ule, Aljaž, Darnell, Robert B.·2003·Science

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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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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.
ORCID: Ule, Jernej
Jensen, Kirk B.
Ruggiu, Matteo
Darnell, Robert B.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2003-11-14
Volume: 302
Issue: 5648
Pages: 1212-1215
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1090095
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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CLIP Identifies Nova-Regulated RNA Networks in the Brain

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