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Sex-specific role for the long noncoding RNA Pnky in mouse behavior

Author

Listed:
  • Parna Saha

    (University of California, San Francisco
    University of California, San Francisco)

  • Rebecca E. Andersen

    (University of California, San Francisco
    University of California, San Francisco
    Boston Children’s Hospital)

  • Sung Jun Hong

    (University of California, San Francisco
    University of California, San Francisco)

  • Eugene Gil

    (University of California, San Francisco
    University of California, San Francisco)

  • Jeffrey Simms

    (Gladstone Institutes)

  • Hyeonseok Choi

    (University of California, Berkeley)

  • Daniel A. Lim

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

Abstract

The aberrant expression of specific long noncoding RNAs (lncRNAs) has been associated with cognitive and psychiatric disorders. Although a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few lncRNAs have been shown to underlie animal behavior. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA can underlie specific behavior by functioning in trans. Male Pnky-knockout mice have decreased context generalization in a paradigm of associative fear learning and memory. In female Pnky-knockout mice, there is an increase in the acoustic startle response, a behavior that is altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome transgene decreases the acoustic startle response in female Pnky-knockout mice, demonstrating that Pnky can modulate specific animal behavior by functioning in trans. More broadly, these studies illustrate how specific lncRNAs can underlie cognitive and mood disorders.

Suggested Citation

  • Parna Saha & Rebecca E. Andersen & Sung Jun Hong & Eugene Gil & Jeffrey Simms & Hyeonseok Choi & Daniel A. Lim, 2024. "Sex-specific role for the long noncoding RNA Pnky in mouse behavior," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50851-7
    DOI: 10.1038/s41467-024-50851-7
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    References listed on IDEAS

    as
    1. Jesse M. Engreitz & Jenna E. Haines & Elizabeth M. Perez & Glen Munson & Jenny Chen & Michael Kane & Patrick E. McDonel & Mitchell Guttman & Eric S. Lander, 2016. "Local regulation of gene expression by lncRNA promoters, transcription and splicing," Nature, Nature, vol. 539(7629), pages 452-455, November.
    2. Neelroop N. Parikshak & Vivek Swarup & T. Grant Belgard & Manuel Irimia & Gokul Ramaswami & Michael J. Gandal & Christopher Hartl & Virpi Leppa & Luis de la Torre Ubieta & Jerry Huang & Jennifer K. Lo, 2016. "Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism," Nature, Nature, vol. 540(7633), pages 423-427, December.
    Full references (including those not matched with items on IDEAS)

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