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Divergent landscapes of A-to-I editing in postmortem and living human brain

Author

Listed:
  • Miguel Rodriguez de los Santos

    (Icahn School of Medicine at Mount Sinai)

  • Brian H. Kopell

    (Icahn School of Medicine at Mount Sinai)

  • Ariela Buxbaum Grice

    (Icahn School of Medicine at Mount Sinai)

  • Gauri Ganesh

    (Icahn School of Medicine at Mount Sinai)

  • Andy Yang

    (Icahn School of Medicine at Mount Sinai)

  • Pardis Amini

    (Icahn School of Medicine at Mount Sinai)

  • Lora E. Liharska

    (Icahn School of Medicine at Mount Sinai)

  • Eric Vornholt

    (Icahn School of Medicine at Mount Sinai)

  • John F. Fullard

    (Icahn School of Medicine at Mount Sinai)

  • Pengfei Dong

    (Icahn School of Medicine at Mount Sinai)

  • Eric Park

    (Icahn School of Medicine at Mount Sinai)

  • Sarah Zipkowitz

    (Icahn School of Medicine at Mount Sinai)

  • Deepak A. Kaji

    (Icahn School of Medicine at Mount Sinai)

  • Ryan C. Thompson

    (Icahn School of Medicine at Mount Sinai)

  • Donjing Liu

    (Icahn School of Medicine at Mount Sinai)

  • You Jeong Park

    (Icahn School of Medicine at Mount Sinai)

  • Esther Cheng

    (Icahn School of Medicine at Mount Sinai)

  • Kimia Ziafat

    (Icahn School of Medicine at Mount Sinai)

  • Emily Moya

    (Icahn School of Medicine at Mount Sinai)

  • Brian Fennessy

    (Icahn School of Medicine at Mount Sinai)

  • Lillian Wilkins

    (Icahn School of Medicine at Mount Sinai)

  • Hannah Silk

    (Icahn School of Medicine at Mount Sinai)

  • Lisa M. Linares

    (Icahn School of Medicine at Mount Sinai)

  • Brendan Sullivan

    (Icahn School of Medicine at Mount Sinai)

  • Vanessa Cohen

    (Icahn School of Medicine at Mount Sinai)

  • Prashant Kota

    (Icahn School of Medicine at Mount Sinai)

  • Claudia Feng

    (Icahn School of Medicine at Mount Sinai)

  • Jessica S. Johnson

    (Icahn School of Medicine at Mount Sinai)

  • Marysia-Kolbe Rieder

    (Icahn School of Medicine at Mount Sinai)

  • Joseph Scarpa

    (Icahn School of Medicine at Mount Sinai)

  • Girish N. Nadkarni

    (Icahn School of Medicine at Mount Sinai)

  • Minghui Wang

    (Icahn School of Medicine at Mount Sinai)

  • Bin Zhang

    (Icahn School of Medicine at Mount Sinai)

  • Pamela Sklar

    (Icahn School of Medicine at Mount Sinai)

  • Noam D. Beckmann

    (Icahn School of Medicine at Mount Sinai)

  • Eric E. Schadt

    (Icahn School of Medicine at Mount Sinai)

  • Panos Roussos

    (Icahn School of Medicine at Mount Sinai)

  • Alexander W. Charney

    (Icahn School of Medicine at Mount Sinai)

  • Michael S. Breen

    (Icahn School of Medicine at Mount Sinai)

Abstract

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49268-z
    DOI: 10.1038/s41467-024-49268-z
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    References listed on IDEAS

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