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Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the
R J Buckanovich1, J B Posner, R B Darnell
1Laboratory of Molecular Neuro-Oncology, Rockefeller, University New York, New York 10021.
Abstract:
Paraneoplastic opsoclonus-ataxia, a disorder of motor control, develops in breast or lung cancer patients who harbor an antibody (Ri) that recognizes their tumors and a nuclear neuronal protein of 55 kd. We have characterized a gene, Nova, encoding an antigen recognized by the Ri antibody. Nova encodes a novel, highly conserved protein, homologous to the RNA-binding protein hnRNP K, the yeast splicing protein MER1, and a motif in several retroviral proteases. Northern blot analysis detects Nova transcripts only in brain, and several alternatively spliced forms are present in brain and tumor cells. Nova expression is restricted to the ventral brain stem and spinal cord in E18 mice. Since Nova encodes a target antigen in the motor disorder paraneoplastic opsoclonus-ataxia that is expressed in the developing subcortical motor system, it is a likely participant in both the pathogenesis of paraneoplastic opsoclonus-ataxia and the developmental biology of the motor system. The homology between Nova and hnRNP K suggests that Nova regulates RNA splicing or metabolism in a specific subset of developing neurons.
Insights
Researchers identified the Nova gene, which encodes a protein targeted by the Ri antibody in paraneoplastic opsoclonus-ataxia. This protein plays a role in motor control disorders and neural development.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Paraneoplastic opsoclonus-ataxia is a motor control disorder linked to breast or lung cancer.
- The Ri antibody targets both tumor antigens and a 55 kd nuclear neuronal protein.
Purpose of the Study:
- To characterize the Nova gene encoding the Ri antibody target antigen.
- To investigate Nova's role in paraneoplastic opsoclonus-ataxia and motor system development.
Main Methods:
- Gene characterization and protein homology analysis.
- Northern blot analysis for Nova transcript detection.
- Expression pattern analysis in developing mouse models.
Main Results:
- The Nova gene encodes a novel, conserved protein homologous to RNA-binding proteins.
- Nova transcripts are found in the brain, with alternative splicing in brain and tumor cells.
- Nova expression is specifically localized to the ventral brain stem and spinal cord in developing mice.
Conclusions:
- Nova is a likely participant in paraneoplastic opsoclonus-ataxia pathogenesis.
- Nova is involved in the developmental biology of the motor system.
- Nova's homology to hnRNP K suggests a role in neuronal RNA metabolism or splicing.