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Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease

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  • Xianjun Dong

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Yunfei Bai

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Southeast University)

  • Zhixiang Liao

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital)

  • David Gritsch

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital)

  • Xiaoli Liu

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Zhejiang Hospital)

  • Tao Wang

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Northwestern Polytechnical University)

  • Rebeca Borges-Monroy

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital)

  • Alyssa Ehrlich

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Brigham and Women’s Hospital, Harvard Medical School)

  • Geidy E. Serrano

    (Banner Sun Health Research Institute)

  • Mel B. Feany

    (Brigham & Women’s Hospital, Harvard Medical School)

  • Thomas G. Beach

    (Banner Sun Health Research Institute)

  • Clemens R. Scherzer

    (Harvard Medical School, Brigham & Women’s Hospital
    Harvard Medical School and Brigham & Women’s Hospital
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network
    Program in Neuroscience, Harvard Medical School)

Abstract

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1526 and 3308 circRNAs are custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 29% of Parkinson’s and 12% of Alzheimer’s disease-associated genes produced validated circRNAs. circDNAJC6, which is transcribed from a juvenile-onset Parkinson’s gene, is already dysregulated during prodromal, onset stages of common Parkinson’s disease neuropathology. Globally, addiction-associated genes preferentially produce circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.

Suggested Citation

  • Xianjun Dong & Yunfei Bai & Zhixiang Liao & David Gritsch & Xiaoli Liu & Tao Wang & Rebeca Borges-Monroy & Alyssa Ehrlich & Geidy E. Serrano & Mel B. Feany & Thomas G. Beach & Clemens R. Scherzer, 2023. "Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40348-0
    DOI: 10.1038/s41467-023-40348-0
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    1. Sebastian Memczak & Marvin Jens & Antigoni Elefsinioti & Francesca Torti & Janna Krueger & Agnieszka Rybak & Luisa Maier & Sebastian D. Mackowiak & Lea H. Gregersen & Mathias Munschauer & Alexander Lo, 2013. "Circular RNAs are a large class of animal RNAs with regulatory potency," Nature, Nature, vol. 495(7441), pages 333-338, March.
    2. Eric L. Nostrand & Peter Freese & Gabriel A. Pratt & Xiaofeng Wang & Xintao Wei & Rui Xiao & Steven M. Blue & Jia-Yu Chen & Neal A. L. Cody & Daniel Dominguez & Sara Olson & Balaji Sundararaman & Liju, 2020. "A large-scale binding and functional map of human RNA-binding proteins," Nature, Nature, vol. 583(7818), pages 711-719, July.
    3. Wanying Wu & Jinyang Zhang & Xiaofei Cao & Zhengyi Cai & Fangqing Zhao, 2022. "Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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    Cited by:

    1. Mateja Rybiczka-Tešulov & Oxana Garritsen & Morten T. Venø & Laura Wieg & Roland van Dijk & Karim Rahimi & Andreia Gomes-Duarte & Marina de Wit & Lieke L. Haar & Lars Michels & Nicky C. H. van Kronenb, 2024. "Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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