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PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease

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  • Xiaobing Huang

    (Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University
    University of Macau)

  • Changliang Wang

    (University of Macau
    Guangzhou Medical University)

  • Tianjiao Zhang

    (University of Macau)

  • Rongzhen Li

    (University of Macau)

  • Liang Chen

    (Shantou University)

  • Ka Lai Leung

    (University of Macau)

  • Merja Lakso

    (University of Macau)

  • Qinghua Zhou

    (Jinan University
    Jinan University)

  • Hongjie Zhang

    (University of Macau)

  • Garry Wong

    (University of Macau)

Abstract

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.

Suggested Citation

  • Xiaobing Huang & Changliang Wang & Tianjiao Zhang & Rongzhen Li & Liang Chen & Ka Lai Leung & Merja Lakso & Qinghua Zhou & Hongjie Zhang & Garry Wong, 2023. "PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41881-8
    DOI: 10.1038/s41467-023-41881-8
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    References listed on IDEAS

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    1. Rachel Kaletsky & Rebecca S. Moore & Geoffrey D. Vrla & Lance R. Parsons & Zemer Gitai & Coleen T. Murphy, 2020. "C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance," Nature, Nature, vol. 586(7829), pages 445-451, October.
    2. Jie Yuan & Si-Yuan Chang & Shi-Gang Yin & Zhi-Yang Liu & Xiu Cheng & Xi-Juan Liu & Qiang Jiang & Ge Gao & De-Ying Lin & Xin-Lei Kang & Shi-Wei Ye & Zheng Chen & Jiang-An Yin & Pei Hao & Lubin Jiang & , 2020. "Two conserved epigenetic regulators prevent healthy ageing," Nature, Nature, vol. 579(7797), pages 118-122, March.
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