First Author | Ule J | Year | 2003 |
Journal | Science | Volume | 302 |
Issue | 5648 | Pages | 1212-5 |
PubMed ID | 14615540 | Mgi Jnum | J:306711 |
Mgi Id | MGI:6718240 | Doi | 10.1126/science.1090095 |
Citation | Ule J, et al. (2003) CLIP identifies Nova-regulated RNA networks in the brain. Science 302(5648):1212-5 |
abstractText | 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. |