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CircGRIA1 shows an age-related increase in male macaque brain and regulates synaptic plasticity and synaptogenesis

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  • Kaiyu Xu

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ying Zhang

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Wandi Xiong

    (Peking University
    Peking University
    Peking-Tsinghua Center for Life Sciences)

  • Zhongyu Zhang

    (Peking University
    Peking University)

  • Zhengbo Wang

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming University of Science and Technology)

  • Longbao Lv

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Primate Research Center of the Chinese Academy of Sciences)

  • Chao Liu

    (Kunming Primate Research Center of the Chinese Academy of Sciences)

  • Zhengfei Hu

    (Kunming Primate Research Center of the Chinese Academy of Sciences)

  • Yong-Tang Zheng

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Primate Research Center of the Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Lin Lu

    (Peking University
    Peking University
    Peking-Tsinghua Center for Life Sciences)

  • Xin-Tian Hu

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Primate Research Center of the Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Jiali Li

    (Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
    Peking University
    Peking University
    Kunming Primate Research Center of the Chinese Academy of Sciences)

Abstract

Circular RNAs (circRNAs) are abundant in mammalian brain and some show age-dependent expression patterns. Here, we report that circGRIA1, a conserved circRNA isoform derived from the genomic loci of α-mino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit Gria1, shows an age-related and male-specific increase in expression in the rhesus macaque prefrontal cortex and hippocampus. We show circGRIA1 is predominantly localized to the nucleus, and find an age-related increase in its association with the promoter region of Gria1 gene, suggesting it has a regulatory role in Gria1 transcription. In vitro and in vivo manipulation of circGRIA1 negatively regulates Gria1 mRNA and protein levels. Knockdown of circGRIA1 results in an age-related improvement of synaptogenesis, and GluR1 activity-dependent synaptic plasticity in the hippocampal neurons in males. Our findings underscore the importance of circRNA regulation and offer an insight into the biology of brain aging.

Suggested Citation

  • Kaiyu Xu & Ying Zhang & Wandi Xiong & Zhongyu Zhang & Zhengbo Wang & Longbao Lv & Chao Liu & Zhengfei Hu & Yong-Tang Zheng & Lin Lu & Xin-Tian Hu & Jiali Li, 2020. "CircGRIA1 shows an age-related increase in male macaque brain and regulates synaptic plasticity and synaptogenesis," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17435-7
    DOI: 10.1038/s41467-020-17435-7
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