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

Autor: Rodriguez de Los Santos M; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Kopell BH; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Buxbaum Grice A; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Ganesh G; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Yang A; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Amini P; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Liharska LE; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Vornholt E; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Fullard JF; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Dong P; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Park E; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Zipkowitz S; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Kaji DA; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Thompson RC; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Liu D; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Park YJ; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Cheng E; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Ziafat K; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Moya E; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Fennessy B; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Wilkins L; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Silk H; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Linares LM; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Sullivan B; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Cohen V; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Kota P; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Feng C; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Johnson JS; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Rieder MK; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Scarpa J; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Nadkarni GN; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Wang M; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Zhang B; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Sklar P; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Beckmann ND; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Schadt EE; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Roussos P; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Charney AW; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Breen MS; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. michael.breen@mssm.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 26; Vol. 15 (1), pp. 5366. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1038/s41467-024-49268-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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