Publication Date:
2003-11-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ule, Jernej -- Jensen, Kirk B -- Ruggiu, Matteo -- Mele, Aldo -- Ule, Aljaz -- Darnell, Robert B -- K01 MH64753/MH/NIMH NIH HHS/ -- NS40955/NS/NINDS NIH HHS/ -- R01 NS34389/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 14;302(5648):1212-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14615540" target="_blank"〉PubMed〈/a〉
Keywords:
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
;
Neurons/*metabolism
;
Precipitin Tests
;
RNA Precursors/genetics/*metabolism
;
RNA, Messenger/genetics/*metabolism
;
RNA-Binding Proteins/*metabolism
;
Reverse Transcriptase Polymerase Chain Reaction
;
Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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