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|Title:||CLIP Identifies Nova-Regulated RNA Networks in the Brain|
|Citation:||Science, 2003; 302(5648):1212-1215|
|Publisher:||Amer Assoc Advancement Science|
|Jernej Ule, Kirk B. Jensen, Matteo Ruggiu, Aldo Mele, Aljaz Ule and Robert B. Darnell.|
|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[sup-/-] mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory 7-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.|
|Keywords:||Brain; Neurons; Animals; Mice; Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase 9; Carrier Proteins; RNA-Binding Proteins; Membrane Proteins; Nerve Tissue Proteins; RNA Precursors; RNA, Messenger; 3' Untranslated Regions; Antigens, Neoplasm; Precipitin Tests; Reverse Transcriptase Polymerase Chain Reaction; Ultraviolet Rays; Alternative Splicing; Neural Inhibition; Introns; Exons|
|Appears in Collections:||Molecular and Biomedical Science publications|
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