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The Neuronal RNA Binding Protein Nova-1 Recognizes Specific RNA Targets In Vitro and In Vivo

Buckanovich, Ronald J., Darnell, Robert B.·1997·Molecular and Cellular Biology
DOI 10.1128/mcb.17.6.3194
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Abstract

Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a disorder associated with breast cancer and motor dysfunction, is a neuron-specific nuclear RNA binding protein. We have identified in vivo Nova-1 RNA ligands by combining affinity-elution-based RNA selection with protein-RNA immunoprecipitation. Starting with a pool of approximately 10(15) random 52-mer RNAs, we identified long stem-loop RNA ligands that bind to Nova-1 with high affinity (Kd of approximately 2 nM). The loop region of these RNAs harbors a approximately 15-bp pyrimidine-rich element [UCAU(N)(0-2)]3 which is essential for Nova-1 binding. Mutagenesis studies defined the third KH domain of Nova-1 and the [UCAU(N)(0-2)]3 element as necessary for in vitro binding. Consensus [UCAU (N)(0-2)], elements were identified in two neuronal pre-mRNAs, one encoding the inhibitory glycine receptor alpha2 (GlyR alpha2) and a second encoding Nova-1 itself. Nova-1 protein binds these RNAs with high affinity and specificity in vitro, and this binding can be blocked by POMA antisera. Moreover, both Nova-1 and GlyR alpha2 pre-mRNAs specifically coimmunoprecipitated with Nova-1 protein from brain extracts. Thus, Nova-1 functions as a sequence-specific nuclear RNA binding protein in vivo; disruption of the specific interaction between Nova-1 and GlyR alpha2 pre-mRNA may underlie the motor dysfunction seen in POMA.

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Metadata

Authors
Buckanovich, R. J., & Darnell, R. B.
Affiliations
Laboratory of Molecular Neuro-Oncology, The Rockefeller University
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
1997-06
Volume
17
Issue
6
Pages
3194-3201
ISSN
1098-5549
DOI
10.1128/mcb.17.6.3194
Cited by
217
References
1
Language
en
Licence
journals.asm.org/non-commercial-tdm-license (tdm)

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CoChat. (2026). Citation check: The Neuronal RNA Binding Protein Nova-1 Recognizes Specific RNA Targets In Vitro and In Vivo. https://app.cochat.ai/papers/10.1128/mcb.17.6.3194
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Buckanovich, R. J., & Darnell, R. B. (1997). The Neuronal RNA Binding Protein Nova-1 Recognizes Specific RNA Targets In Vitro and In Vivo. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.17.6.3194