RNA-binding protein Nova-1 (NOVA1)

RNA-binding protein Nova-1 (NOVA1) is a neuron-specific RNA-binding protein expressed predominantly in the central nervous system where it regulates alternative splicing of pre-mRNAs in a sequence-specific manner. NOVA1 is a member of the Nova family of paraneoplastic disease antigens and functions primarily through three KH domains that mediate high-affinity RNA binding, especially to YCAY motifs within target transcripts. It is essential for normal neural development, neuromuscular control, and survival in mammals. NOVA1 is also recognized as an oncogenic factor in glioblastoma, where its overexpression antagonizes microRNA actions (AGO2-miRNA) and upregulates cholesterol synthesis, promoting tumor cell viability. It is a known autoantigen in paraneoplastic neurologic syndromes, particularly opsoclonus-myoclonus ataxia, where antibody-mediated inhibition of its RNA binding contributes to disease pathology. Genetic and functional perturbations highlight its importance in neural gene regulation, and alterations or deletions in NOVA1 are associated with human neurodevelopmental disorders.

Other names

NOVA alternative splicing regulator 1Nova-1Neuro-oncological ventral antigen 1Onconeural ventral antigen 1Paraneoplastic Ri antigenVentral neuron-specific protein 1

Inhibition of NOVA1-RNA interactions (via antisense oligonucleotides); Potential modulation via immune response targeting NOVA1 as an autoantigen in paraneoplastic conditions