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 gamma-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.
Authors	Jernej Ule, Kirk B Jensen, Matteo Ruggiu, Aldo Mele, Aljaz Ule, Robert B Darnell
Journal	Science (New York, N.Y.) (Science) Vol. 302 Issue 5648 Pg. 1212-5 (Nov 14 2003) ISSN: 1095-9203 [Electronic] United States
PMID	14615540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	3' Untranslated Regions Antigens, Neoplasm Carrier Proteins Membrane Proteins Nerve Tissue Proteins Neuro-Oncological Ventral Antigen RNA Precursors RNA, Messenger RNA-Binding Proteins gephyrin neogenin Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinases
Topics	3' Untranslated Regions Alternative Splicing Animals Antigens, Neoplasm Brain (metabolism) Carrier Proteins (genetics, metabolism) Exons Introns Membrane Proteins (genetics, metabolism) Mice Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinases (genetics, metabolism) Nerve Tissue Proteins (metabolism) Neural Inhibition Neuro-Oncological Ventral Antigen Neurons (metabolism) Precipitin Tests RNA Precursors (genetics, metabolism) RNA, Messenger (genetics, metabolism) RNA-Binding Proteins (metabolism) Reverse Transcriptase Polymerase Chain Reaction Ultraviolet Rays

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