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Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue

Author

Listed:
  • Yiyi Ma

    (Columbia University Medical Center)

  • Eric B. Dammer

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Daniel Felsky

    (Centre for Addiction and Mental Health
    University of Toronto)

  • Duc M. Duong

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Hans-Ulrich Klein

    (Columbia University Medical Center)

  • Charles C. White

    (Broad Institute)

  • Maotian Zhou

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Benjamin A. Logsdon

    (Sage Bionetworks)

  • Cristin McCabe

    (Broad Institute)

  • Jishu Xu

    (Rush University Medical Center)

  • Minghui Wang

    (Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place
    Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place)

  • Thomas S. Wingo

    (Emory University School of Medicine
    Emory University School of Medicine
    Emory University School of Medicine)

  • James J. Lah

    (Emory University School of Medicine
    Emory University School of Medicine)

  • Bin Zhang

    (Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place
    Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place)

  • Julie Schneider

    (Rush University Medical Center)

  • Mariet Allen

    (Mayo Clinic Florida, Department of Neuroscience)

  • Xue Wang

    (Mayo Clinic Florida, Department of Health Sciences Research)

  • Nilüfer Ertekin-Taner

    (Mayo Clinic Florida, Department of Neuroscience
    Mayo Clinic Florida, Department of Neurology)

  • Nicholas T. Seyfried

    (Emory University School of Medicine
    Emory University School of Medicine
    Emory University School of Medicine)

  • Allan I. Levey

    (Emory University School of Medicine
    Emory University School of Medicine)

  • David A. Bennett

    (Rush University Medical Center)

  • Philip L. De Jager

    (Columbia University Medical Center
    Broad Institute)

Abstract

RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer’s disease (AD). Here, we analyzed data from 1,865 brain samples covering 9 brain regions from 1,074 unrelated subjects on a transcriptome-wide scale to identify inter-regional differences in RNA editing. We expand the list of known brain editing events by identifying 58,761 previously unreported events. We note that only a small proportion of these editing events are found at the protein level in our proteome-wide validation effort. We also identified the occurrence of editing events associated with AD dementia, neuropathological measures and longitudinal cognitive decline in: SYT11, MCUR1, SOD2, ORAI2, HSDL2, PFKP, and GPRC5B. Thus, we present an extended reference set of brain RNA editing events, identify a subset that are found to be expressed at the protein level, and extend the narrative of transcriptomic perturbation in AD to RNA editing.

Suggested Citation

  • Yiyi Ma & Eric B. Dammer & Daniel Felsky & Duc M. Duong & Hans-Ulrich Klein & Charles C. White & Maotian Zhou & Benjamin A. Logsdon & Cristin McCabe & Jishu Xu & Minghui Wang & Thomas S. Wingo & James, 2021. "Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27204-9
    DOI: 10.1038/s41467-021-27204-9
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    1. Martin Vaeth & Jun Yang & Megumi Yamashita & Isabelle Zee & Miriam Eckstein & Camille Knosp & Ulrike Kaufmann & Peter Karoly Jani & Rodrigo S. Lacruz & Veit Flockerzi & Imre Kacskovics & Murali Prakri, 2017. "ORAI2 modulates store-operated calcium entry and T cell-mediated immunity," Nature Communications, Nature, vol. 8(1), pages 1-17, April.
    2. Meng How Tan & Qin Li & Raghuvaran Shanmugam & Robert Piskol & Jennefer Kohler & Amy N. Young & Kaiwen Ivy Liu & Rui Zhang & Gokul Ramaswami & Kentaro Ariyoshi & Ankita Gupte & Liam P. Keegan & Cyril , 2017. "Dynamic landscape and regulation of RNA editing in mammals," Nature, Nature, vol. 550(7675), pages 249-254, October.
    3. Makoto Tsuda & Yukari Shigemoto-Mogami & Schuichi Koizumi & Akito Mizokoshi & Shinichi Kohsaka & Michael W. Salter & Kazuhide Inoue, 2003. "P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury," Nature, Nature, vol. 424(6950), pages 778-783, August.
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    1. Miguel Rodriguez de los Santos & Brian H. Kopell & Ariela Buxbaum Grice & Gauri Ganesh & Andy Yang & Pardis Amini & Lora E. Liharska & Eric Vornholt & John F. Fullard & Pengfei Dong & Eric Park & Sara, 2024. "Divergent landscapes of A-to-I editing in postmortem and living human brain," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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