NOVA, THE PARANEOPLASTIC RI ANTIGEN, IS HOMOLOGOUS TO AN RNA-BINDING PROTEIN AND IS SPECIFICALLY EXPRESSED IN THE DEVELOPING MOTOR SYSTEM

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 spicing 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.