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

Nat Commun. 2021 Dec 2;12(1):7035. doi: 10.1038/s41467-021-27204-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Atlases as Topic
  • Brain / metabolism
  • Brain / pathology
  • Brain Chemistry
  • Gene Expression Profiling
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • ORAI2 Protein / genetics*
  • ORAI2 Protein / metabolism
  • Phosphofructokinase-1, Type C / genetics
  • Phosphofructokinase-1, Type C / metabolism
  • RNA / genetics*
  • RNA / metabolism
  • RNA Editing*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Synaptotagmins / genetics*
  • Synaptotagmins / metabolism
  • Transcriptome*

Substances

  • GPRC5B protein, human
  • MCUR1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • ORAI2 Protein
  • ORAI2 protein, human
  • Receptors, G-Protein-Coupled
  • SYT11 protein, human
  • Synaptotagmins
  • RNA
  • HSDL2 protein, human
  • Hydroxysteroid Dehydrogenases
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Phosphofructokinase-1, Type C
  • PFKP protein, human

Grant support