Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a disorder associated with breast cancer and motor dysfunction, is a neuron-specific nuclear RNA binding protein. We have identified in vivo Nova-1 RNA ligands by combining affinity-elution-based RNA selection with protein-RNA immunoprecipitation. Starting with a pool of approximately 10(15) random 52-mer RNAs, we identified long stem-loop RNA ligands that bind to Nova-1 with high affinity (Kd of approximately 2 nM). The loop region of these RNAs harbors a approximately 15-bp pyrimidine-rich element [UCAU(N)(0-2)]3 which is essential for Nova-1 binding. Mutagenesis studies defined the third KH domain of Nova-1 and the [UCAU(N)(0-2)]3 element as necessary for in vitro binding. Consensus [UCAU (N)(0-2)], elements were identified in two neuronal pre-mRNAs, one encoding the inhibitory glycine receptor alpha2 (GlyR alpha2) and a second encoding Nova-1 itself. Nova-1 protein binds these RNAs with high affinity and specificity in vitro, and this binding can be blocked by POMA antisera. Moreover, both Nova-1 and GlyR alpha2 pre-mRNAs specifically coimmunoprecipitated with Nova-1 protein from brain extracts. Thus, Nova-1 functions as a sequence-specific nuclear RNA binding protein in vivo; disruption of the specific interaction between Nova-1 and GlyR alpha2 pre-mRNA may underlie the motor dysfunction seen in POMA.
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PMID:The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro and in vivo. 915 18

Despite circumstantial evidence that opsoclonus-myoclonus (OM) is often immune mediated, no specific autoantigen has been identified. Using sera of 21 patients with several types of OM (idiopathic, associated to small cell lung cancer, and associated to neuroblastoma), we probed a brainstem cDNA library to isolate target neuronal antigens. Thirty-seven clones coding for 25 proteins were isolated, with two groups of autoantigens emerging: (1) proteins of the postsynaptic density, among them the adenomatous polyposis coli, and 2) proteins with expression or function restricted to neurons, including RNA or DNA-binding proteins and zinc-finger proteins. Usually, each patient's serum recognized a different autoantigen, except for adenomatous polyposis coli that was recognized by sera of two patients with idiopathic OM and two control patients with nystagmus, diplopia, and paraneoplastic brainstem dysfunction. Overall, in the indicated types of OM, (1) we found frequent and heterogeneous immunity to neuronal autoantigens without a single specific antibody marker of OM, (2) the occasional detection of antibodies to known onconeuronal antigens (ie, Hu proteins) probably is related to cancer-induced immunity rather than to OM, and (3) the postsynaptic density is a frequent source of novel autoantigens, with several proteins of this complex targeted by antibodies of OM patients.
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PMID:Autoantigen diversity in the opsoclonus-myoclonus syndrome. 1260 2

Childhood opsoclonus-myoclonus syndrome can occur with or without associated neuroblastoma. An autoimmune pathogenesis has been discussed for both forms. We show here that the majority of children with opsoclonus-myoclonus syndrome (10/14) have autoantibodies binding to the surface of isolated rat cerebellar granular neurons. In some patients, these antibodies are masked by IgG binding to ubiquitous surface antigens, which could be removed by preincubation with the nonneuronal control cell line HEK 293. A newly introduced competitive binding assay showed that the surface binding is directed against the same autoantigen in different patients. Therefore, we hypothesize that opsoclonus-myoclonus syndrome may be the result of an autoimmune process against a neuronal surface protein.
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PMID:Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome. 1598 49