A-to-I RNA Editing: Effects on Proteins Key to Neural Excitability

Abstract

RNA editing by adenosine deamination is a process used to diversify the proteome. The expression of ADARs, the editing enzymes, is ubiquitous among true metazoans, and so adenosine deamination is thought to be universal. By changing codons at the level of mRNA, protein function can be altered, perhaps in response to physiological demand. Although the number of editing sites identified in recent years has been rising exponentially, their effects on protein function, in general, are less well understood. This review assesses the state of the field and highlights particular cases where the biophysical alterations and functional effects caused by RNA editing have been studied in detail.

Adenosine Deaminase That Acts on RNA 3 (ADAR3) Binding to Glutamate Receptor Subunit B Pre-mRNA Inhibits RNA Editing in Glioblastoma

“…A majority of the targets of RNA editing are found in the nervous system, and RNA editing is critical for maintaining proper neuronal function (10). Furthermore, transcripts encoding proteins involved in neurotransmission are often targets of RNA editing, which alters the protein amino acid sequence and physiological function of these ion channels and receptors (11,12).…”

“…A majority of the targets of RNA editing are found in the nervous system, and RNA editing is critical for maintaining proper neuronal function (10). Furthermore, transcripts encoding proteins involved in neurotransmission are often targets of RNA editing, which alters the protein amino acid sequence and physiological function of these ion channels and receptors (11,12).In mammals, three ADAR proteins, ADAR1, ADAR2, and ADAR3, and two ADAR-like proteins, ADAD1 and ADAD2, have been identified (13-17). The ADAR and ADAR-like protein family members contain several common modular domains that are important for function (18,19).…”

Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing

“…When editing occurs in coding regions of mRNAs, inosine is read as guanosine (7), often causing codons to change in a process that resembles a natural system for site-directed mutagenesis. As expected from a mechanism that can recode almost half of all codons, the effects of RNA editing on protein function are diverse (8). The beststudied examples come from mRNAs encoding elements of the machinery for excitability in the nervous system, where editing changes ion selectivity of ionotropic glutamate receptors, G-protein coupling of metabotropic serotonin receptors, inactivation of a voltage-dependent K + channel, and the transport rate of a Na + /K + ATPase, among other things (9)(10)(11)(12).…”

Antagonistic and stimulative roles of ADAR1 in RNA silencing

“…[1][2][3] In a few cases, A-to-I RNA editing of mRNA results in recoding and functional diversification of a select group of neurotransmitters and ion channels. [4][5][6] However, A-to-I editing occurs most frequently in non-coding regions that contain repetitive elements such as SINE and LINE. [7][8][9][10][11][12] The biological significance of repetitive RNA editing is largely unknown.…”