CLIP Identifies Nova-Regulated RNA Networks in the Brain

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

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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-aminobutydc 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.

Original languageEnglish
Pages (from-to)1212-1215
Number of pages4
JournalScience
Volume302
Issue number5648
DOIs
Publication statusPublished - 14 Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • General

Cite this

Ule, J., Jensen, K. B., Ruggiu, M., Mele, A., Ule, A., & Darnell, R. B. (2003). CLIP Identifies Nova-Regulated RNA Networks in the Brain. Science, 302(5648), 1212-1215. https://doi.org/10.1126/science.1090095