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<p>Natural antisense transcripts (NATs) are important spatial and temporal regulators of gene expression. We previously cloned a NAT (<i>Nat9a)</i> to <i>Scn9a</i>, which encodes the Na<sub>V</sub>1.7 voltage-gated sodium channel that is essential for pain perception. By studying a novel <i>Nat9a</i> global knockout mouse model, we demonstrate that the deletion of <i>Nat9a</i> does not affect pain sensitivity but instead partially impairs motor coordination. We show that <i>Nat9a</i> is expressed throughout the peripheral and central nervous systems and its expression is enriched, but not limited to, cells that express parvalbumin (<i>Pvalb),</i> which is a marker for proprioceptors in DRG and a subclass of interneurons in spinal cord and brain. <i>Nat9a</i> knockout leads to an increase in <i>Scn9a</i> expression, confirming <i>Nat9a</i>’s physiological role as a negative regulator of <i>Scn9a</i>. Furthermore, CRISPR activation of <i>Nat9a</i> transcription in Cad cells suppresses endogenous <i>Scn9a</i> expression. Notably <i>Nat9a</i> expression in <i>Pvalb</i> + neurons coincides with that of the <i>Scn1a</i> gene (Na<sub>V</sub>1.1 sodium channel) with both genes sharing a divergent bi-part promoter region. This suggests a mechanism by which <i>Nat9a</i> transcription leads to suppression of <i>Scn9a</i> and promotes neuronal expression of Na<sub>V</sub>1.1 over Na<sub>V</sub>1.7.</p>

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Natural antisense transcript Nat9a suppresses Scn9a (NaV1.7) expression in parvalbumin-positive proprioceptive and inhibitory neurons

  • 期刊论文

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  • 发表日期：

    2026年4月16日

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  • Shengnan Li,
  • Sonia Santana-Varela,
  • Hajar Mikaeili,
  • Abdella M. Habib,
  • Janvi Patel,
  • Naxi Tian,
  • Andrei L. Okorokov,
  • James J. Cox

摘要

Natural antisense transcripts (NATs) are important spatial and temporal regulators of gene expression. We previously cloned a NAT (Nat9a) to Scn9a, which encodes the NaV1.7 voltage-gated sodium channel that is essential for pain perception. By studying a novel Nat9a global knockout mouse model, we demonstrate that the deletion of Nat9a does not affect pain sensitivity but instead partially impairs motor coordination. We show that Nat9a is expressed throughout the peripheral and central nervous systems and its expression is enriched, but not limited to, cells that express parvalbumin (Pvalb), which is a marker for proprioceptors in DRG and a subclass of interneurons in spinal cord and brain. Nat9a knockout leads to an increase in Scn9a expression, confirming Nat9a’s physiological role as a negative regulator of Scn9a. Furthermore, CRISPR activation of Nat9a transcription in Cad cells suppresses endogenous Scn9a expression. Notably Nat9a expression in Pvalb + neurons coincides with that of the Scn1a gene (NaV1.1 sodium channel) with both genes sharing a divergent bi-part promoter region. This suggests a mechanism by which Nat9a transcription leads to suppression of Scn9a and promotes neuronal expression of NaV1.1 over NaV1.7.