RNA editing in brain controls a determinant of ion flow in glutamate-gated channels
Abstract
L-glutamate, the principal excitatory transmitter in the brain, gates ion channels mediating fast neurotransmission. Subunit components of two related classes of glutamate receptor channels have been characterized by cDNA cloning and shown to carry either an arginine or a glutamine residue in a defined position of their putative channel-forming segment. The arginine residue in this segment profoundly alters, and dominates, the properties of ion flow, as demonstrated for one channel class. We now show that the genomic DNA sequences encoding the particular channel segment of all subunits harbor a glutamine codon (CAG), even though an arginine codon (CGG) is found in mRNAs of three subunits. Multiple genes and alternative exons were excluded as sources for the arginine codon; hence, we propose that transcripts for three subunits are altered by RNA editing. This process apparently edits subunit transcripts of the two glutamate receptor classes with different efficiency and selectivity.
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Four of these genes were involved in AD-related pathways such as Ca2+ permeability [GRIA2 and GRIK2], cellular dysfunction, and protein stability [NOVA1 and GIPC1].
“Four of these genes were involved in AD-related pathways such as Ca2+ permeability [GRIA2 (55) and GRIK2 (29)], cellular dysfunction, and protein stability [NOVA1 (56) and GIPC1 (57)].”
From Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains (2025) · cites this paper as [55]
In BM36, altered A-to-I editing sites include GRIA2 (R/G and Q/R), GRIK2 (Q/R), and NOVA1 (S/G).
“For example, in BM36, we identified well characterized A-to-I editing sites of GRIA2 (R/G and Q/R) (55, 75, 76) and GRIK2 (Q/R) (29, 77), as well as previously reported editing sites in NOVA1 (S/G) (29, 56) (Fig. 5D).”
From Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains (2025) · cites this paper as [55]
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- Authors
- Sommer, B., Köhler, M., Sprengel, R., & Seeburg, P. H.
- Affiliations
- Heidelberg University (DE)
- Max Planck Society (DE)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1991-10
- Volume
- 67
- Issue
- 1
- Pages
- 11-19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2056025481
- Cited by
- 1,517
- References
- 1
- Citations by year
- 2026: 29 · 2025: 41 · 2024: 40 · 2023: 43 · 2022: 36 · 2021: 46 · 2020: 46 · 2019: 39 · 2018: 39 · 2017: 48 · 2016: 30 · 2015: 27 · 2014: 41 · 2013: 43 · 2012: 45
- FWCI
- 21.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Bundesministerium für Forschung und Technologie (BCT 364 AZ 231/7291)
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft (B9, SFB 317)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- RNA editing, glutamate receptors, channel gating, arginine codons, ion flow, excitatory neurotransmission, alternative splicing, glutamate-gated channels
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Brain, Cloning, Molecular, Codon, Exons, Glutamates, Glutamine, Kainic Acid, Liver, Mice, Inbred C57BL, Molecular Sequence Data, Oligodeoxyribonucleotides, Oxadiazoles, RNA, RNA, Messenger, Ion Channel Gating, Genomic Library, Polymerase Chain Reaction, Receptors, Glutamate, Receptors, Neurotransmitter, Receptors, AMPA, Kainic Acid Receptors, Glutamic Acid, Mice
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