CLIP identifies Nova-regulated RNA networks in the brain.
Science
; 302(5648): 1212-5, 2003 Nov 14.
Article
in En
| MEDLINE
| ID: mdl-14615540
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.
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Database:
MEDLINE
Main subject:
Brain
/
RNA, Messenger
/
RNA Precursors
/
RNA-Binding Proteins
/
Antigens, Neoplasm
/
Nerve Tissue Proteins
/
Neurons
Limits:
Animals
Language:
En
Journal:
Science
Year:
2003
Type:
Article
Affiliation country:
United States