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

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 J. Lah, Bin Zhang, Julie Schneider, Mariet Allen, Xue Wang, Nilüfer Ertekin-Taner, Nicholas T. Seyfried, Allan I. LeveyDavid A. Bennett, Philip L. De Jager

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number7035
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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