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PMID: 9789075 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 22 ·1998-10-27 ·Pages 13254-9

Yang YY, Yin GL, Darnell RB

Abstract

Paraneoplastic opsoclonus myoclonus ataxia (POMA) is a neurologic disorder thought to be mediated by an autoimmune attack against onconeural disease antigens that are expressed by gynecologic or lung tumors and by neurons. One POMA disease antigen, termed Nova-1, has been identified as a neuron-specific KH-type RNA-binding protein. Nova-1 expression is restricted to specific regions of the central nervous system, primarily the hindbrain and ventral spinal cord, which correlate with the predominantly motor symptoms in POMA. However, POMA antisera recognize antigens that are widely expressed in both caudal and rostral regions of the central nervous system, and some patients develop cognitive symptoms. We have used POMA antisera to clone a cDNA encoding a second POMA disease antigen termed Nova-2. Nova-2 is closely related to Nova-1, and is expressed at high levels in neurons during development and in adulthood, and at lower levels in the adult lung. In the postnatal mouse brain, Nova-2 is expressed in a pattern that is largely reciprocal with Nova-1, including high levels of Nova-2 expression in the neocortex and hippocampus. Functional characterization of Nova-2 in RNA selection and nitrocellulose filter-binding assays reveals that Nova-2 binds RNA with high affinity and with sequence specificity that differs from Nova-1. Our results demonstrate that the immune response in POMA targets a family of highly related sequence-specific neuronal RNA-binding proteins. The expression pattern of the Nova-2 protein is likely to underlie the development of cognitive deficits in some POMA patients.

MeSH Terms
Amino Acid Sequence Animals Animals, Newborn Antigens, Neoplasm Autoantigens/chemistry,genetics,metabolism Base Sequence Binding Sites Brain/growth & development,metabolism,pathology Dementia/genetics,metabolism,pathology Gene Expression Regulation, Developmental Humans Mice Molecular Sequence Data Nerve Tissue Proteins/biosynthesis,genetics Neuro-Oncological Ventral Antigen Ocular Motility Disorders/genetics,metabolism,pathology Oligoribonucleotides/metabolism Paraneoplastic Syndromes/genetics,metabolism,pathology RNA-Binding Proteins/chemistry,genetics,metabolism Ribonucleoproteins/chemistry,genetics,metabolism Sequence Alignment Sequence Homology, Amino Acid
Chemicals
Antigens, Neoplasm Autoantigens Nerve Tissue Proteins Neuro-Oncological Ventral Antigen Oligoribonucleotides RNA-Binding Proteins Ribonucleoproteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yang Y Y
Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, NY 10021, USA.
Yin G L
Darnell R B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.22.13254
Published
1998-10-27
Pages
13254-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23773
Subset
IM
Grants
NINDS NIH HHS · R01 NS34389 · United States
NCI NIH HHS · CA 09673-18 · United States
NINDS NIH HHS · R01 NS034389 · United States
NCI NIH HHS · T32 CA009673 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIGMS NIH HHS · 2T32 GM07739 · United States
Databases
GENBANK
AF083898
External Links
PubMed source DOI: 10.1073/pnas.95.22.13254 PMC Full Text View journal details
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