Title

The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies

Author

Buckanovich RJ; Yang YY; Darnell RB

Address

Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, New York 10021, USA

Source

J Neurosci, 16(3):1114-22 1996 Feb 1

Abstract

Nova-1, a protein expressed in tumors and neurons, is a target antigen in a human paraneoplastic motor disorder [paraneoplastic opsoclonus-myoclonus ataxia (POMA)]. We evaluated the relationship between the function of Nova-1 and its role as a disease antigen. We show that Nova-1 is a neuron-specific RNA-binding protein with sequence and functional similarities to FMR-1. Nova-1 mRNA is restricted to the subcortical nervous system, and the protein binds to RNA with high affinity. Nova-1 KH domains mediate this RNA binding, and point mutations within them abrogate binding. POMA disease antisera (6/6) recognize the third KH domain but not an inactive point mutant, and affinity-purified antibody blocks Nova-1 RNA binding. Thus, a cardinal feature of POMA is the production of antibodies that inhibit Nova-1-RNA interactions, suggesting such inhibition may cause the neurological disease.

Language

English

Unique Identifier

96140368

MESH Headings

Amino Acid Sequence ; Animal ; Antibodies, Neoplasm *IM ; Antigens, Neoplasm CH/GE/IM/*PH ; Ataxia ET/*IM ; Autoantibodies *IM ; Autoimmune Diseases IM ; Brain Chemistry ; Consensus Sequence ; Epitopes IM ; Human ; Mice ; Molecular Sequence Data ; Myoclonus ET/*IM ; Neoplasms CO/IM ; Nerve Tissue Proteins AI/CH/GE/IM/*PH ; Neurons *ME ; Ocular Motility Disorders ET/*IM ; Paraneoplastic Syndromes *IM ; Point Mutation ; Protein Binding ; Protein Structure, Tertiary ; Ribonucleoproteins AI/CH/GE/IM/*PH ; RNA-Binding Proteins AI/CH/GE/IM/*PH ; Sequence Alignment ; Sequence Homology, Amino Acid ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL  ARTICLE

ISSN

0270-6474

Country of Publication

UNITED STATES

CAS Registry Number

0 (Antibodies, Neoplasm); 0 (Antigens, Neoplasm); 0 (Autoantibodies); 0 (Epitopes); 0 (Nerve Tissue Proteins); 0 (Nova antigen); 0 (Ribonucleoproteins); 0 (RNA-Binding Proteins)