title: Activity-regulated RNA editing in select neuronal subfields in hippocampus.
abstract: RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa. In addition to modifications in non-coding regions, editing contributes to diversification of protein function, in analogy to alternative splicing. However, although splicing programs respond to external signals, facilitating fine tuning and homeostasis of cellular functions, a similar regulation has not been described for RNA editing. Here, we show that the AMPA receptor R/G editing site is dynamically regulated in the hippocampus in response to activity. These changes are bi-directional, reversible and correlate with levels of the editase Adar2. This regulation is observed in the CA1 hippocampal subfield but not in CA3 and is thus subfield/celltype-specific. Moreover, alternative splicing of the flip/flop cassette downstream of the R/G site is closely linked to the editing state, which is regulated by Ca(2+). Our data show that A-to-I RNA editing has the capacity to tune protein function in response to external stimuli.
authors.affiliation: Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
authors.forename: Ales
authors.initials: A
authors.lastname: Balik
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Penn
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Nemoda
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Greger
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D017393:RNA Editing; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; C104722:glutamate receptor ionotropic, AMPA 2