Cited by 426RNA Research and SplicingRNA regulation and diseaseAmyotrophic Lateral Sclerosis Research

Nova-1 Regulates Neuron-Specific Alternative Splicing and Is Essential for Neuronal Viability

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Jensen, Kirk B, Dredge, B.Kate, Stefani, Giovanni, Zhong, Ru, Buckanovich, Ronald J, Okano, Hirotaka J, Yang, Yolanda Y.L, Darnell, Robert B·2000·Neuron

Abstract

We have combined genetic and biochemical approaches to analyze the function of the RNA-binding protein Nova-1, the paraneoplastic opsoclonus-myoclonus ataxia (POMA) antigen. Nova-1 null mice die postnatally from a motor deficit associated with apoptotic death of spinal and brainstem neurons. Nova-1 null mice show specific splicing defects in two inhibitory receptor pre-mRNAs, glycine alpha2 exon 3A (GlyRalpha2 E3A) and GABA(A) exon gamma2L. Nova protein in brain extracts specifically bound to a previously identified GlyRalpha2 intronic (UCAUY)3 Nova target sequence, and Nova-1 acted directly on this element to increase E3A splicing in cotransfection assays. We conclude that Nova-1 binds RNA in a sequence-specific manner to regulate neuronal pre-mRNA alternative splicing; the defect in splicing in Nova-1 null mice provides a model for understanding the motor dysfunction in POMA.

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Crossref · 10.1016/s0896-6273(00)80900-9

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  • NOVA1 is an interactor of ELAVL4, a gene that codes for a neuronal-specific RNA-binding protein and might have been under positive selection in humans.

    “NOVA1101, which is an interactor of ELAVL4102, a gene that codes for a neuronal-specific RNA-binding protein and might have been under positive selection in humans33,36.”
  • Nova1/2 dKO mice, but not single-knockout mice, show fewer acetylcholine receptor clusters and a loss of apposition between AChR clusters and phrenic nerve terminals.

    “the dKO mice, but not the single-knockout mice, show fewer acetylcholine receptor (AChR) clusters and a loss of apposition between AChR clusters and phrenic nerve terminals”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [38]

  • Nova1−/− mice appear normal at birth but die in the second postnatal week with motor neuron apoptosis, profound motor failure and action-induced tremors.

    “Nova1−/− mice appear normal at birth, but die in the second postnatal week with motor neuron apoptosis, profound motor failure and action-induced tremors37,38.”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [38]

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Authors
Jensen, K. B., Dredge, B. K., Stefani, G., Zhong, R., Buckanovich, R. J., Okano, H. J., Yang, Y. Y. L., & Darnell, R. B.
Affiliations
Rockefeller University (US)
Corresponding author
Darnell, Robert B
Venue
Neuron
Publisher
Elsevier BV
Published
2000-02
Volume
25
Issue
2
Pages
359-371
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2073654740
Cited by
426
References
83
Citations by year
2026: 8 · 2025: 10 · 2024: 10 · 2023: 18 · 2022: 20 · 2021: 7 · 2020: 11 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 14 · 2014: 18 · 2013: 17 · 2012: 13
FWCI
8.67
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01 NS34389, R01NS034389)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
RNA-binding proteins, alternative splicing, neuronal viability, neuronal apoptosis, RNA binding specificity, motor impairment
MeSH terms
Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Brain Chemistry, Brain Stem, Cell Survival, Exons, Genotype, Mice, Inbred C57BL, Motor Neurons, Nerve Tissue Proteins, Protein Binding, Receptors, GABA-A, Ribonucleoproteins, RNA Precursors, Spinal Cord, RNA-Binding Proteins, Apoptosis, Gene Deletion, Alternative Splicing, Receptors, Glycine, Mice, Knockout, Gene Expression Regulation, Developmental, In Situ Nick-End Labeling, Mice

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