Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability

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

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285 Citations (Scopus)

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 α2 exon 3A (GlyRα2 E3A) and GABA(A) exon γ2L. Nova protein in brain extracts specifically bound to a previously identified GlyRα2 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.

Original languageEnglish
Pages (from-to)359-371
Number of pages13
JournalNeuron
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Jan 2000

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Jensen, K., Dredge, B. K., Stefani, G., Zhong, R., Buckanovich, R. J., Okano, H. J., ... Darnell, R. B. (2000). Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron, 25(2), 359-371. https://doi.org/10.1016/S0896-6273(00)80900-9