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ARTICLE

Neuronal Expression of Neural Nitric Oxide Synthase (nNOS) Protein Is Suppressed by an Antisense RNA Transcribed from an NOS Pseudogene

Sergei A. Korneev, Ji-Ho Park and Michael O’Shea
Journal of Neuroscience 15 September 1999, 19 (18) 7711-7720; DOI: https://doi.org/10.1523/JNEUROSCI.19-18-07711.1999
Sergei A. Korneev
1Sussex Centre for Neuroscience, School of Biological Sciences, University of Sussex, Brighton, East Sussex, BN1 9QG, United Kingdom
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Ji-Ho Park
1Sussex Centre for Neuroscience, School of Biological Sciences, University of Sussex, Brighton, East Sussex, BN1 9QG, United Kingdom
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Michael O’Shea
1Sussex Centre for Neuroscience, School of Biological Sciences, University of Sussex, Brighton, East Sussex, BN1 9QG, United Kingdom
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Abstract

Here, we show that a nitric oxide synthase (NOS) pseudogene is expressed in the CNS of the snail Lymnaea stagnalis. The pseudo-NOS transcript includes a region of significant antisense homology to a previously reported neuronal NOS (nNOS)-encoding mRNA. This suggested that the pseudo-NOS transcript acts as a natural antisense regulator of nNOS protein synthesis. In support of this, we show that both the nNOS-encoding and the pseudo-NOS transcripts are coexpressed in giant identified neurons (the cerebral giant cells) in the cerebral ganglion. Moreover, reverse transcription-PCR experiments on RNA isolated from the CNS establish that stable RNA–RNA duplex molecules do form between the two transcripts in vivo. Using an in vitro translation assay, we further demonstrate that the antisense region of the pseudogene transcript prevents the translation of nNOS protein from the nNOS-encoding mRNA. By analyzing NOS RNA and nNOS protein expression in two different identified neurons, we find that when both the nNOS-encoding and the pseudo-NOS transcripts are present in the same neuron, nNOS enzyme activity is substantially suppressed. Importantly, these results show that a natural antisense mechanism can mediate the translational control of nNOS expression in the Lymnaea CNS. Our findings also suggest that transcribed pseudogenes are not entirely without purpose and are a potential source of a new class of regulatory gene in the nervous system.

  • nNOS
  • antisense
  • pseudogene
  • translational regulation
  • dsRNA
  • RNA interface
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The Journal of Neuroscience: 19 (18)
Journal of Neuroscience
Vol. 19, Issue 18
15 Sep 1999
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Neuronal Expression of Neural Nitric Oxide Synthase (nNOS) Protein Is Suppressed by an Antisense RNA Transcribed from an NOS Pseudogene
Sergei A. Korneev, Ji-Ho Park, Michael O’Shea
Journal of Neuroscience 15 September 1999, 19 (18) 7711-7720; DOI: 10.1523/JNEUROSCI.19-18-07711.1999

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Neuronal Expression of Neural Nitric Oxide Synthase (nNOS) Protein Is Suppressed by an Antisense RNA Transcribed from an NOS Pseudogene
Sergei A. Korneev, Ji-Ho Park, Michael O’Shea
Journal of Neuroscience 15 September 1999, 19 (18) 7711-7720; DOI: 10.1523/JNEUROSCI.19-18-07711.1999
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Keywords

  • nNOS
  • antisense
  • pseudogene
  • translational regulation
  • dsRNA
  • RNA interface

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