Transcript Diversification in the Nervous System: A to I RNA Editing in CNS Function and Disease Development

Abstract

RNA editing by adenosine deaminases that act on RNA converts adenosines to inosines in coding and non-coding regions of mRNAs. Inosines are interpreted as guanosines and hence, this type of editing can change codons, alter splice patterns, or influence the fate of an RNA. A to I editing is most abundant in the central nervous system (CNS). Here, targets for this type of nucleotide modification frequently encode receptors and channels. In many cases, the editing-induced amino acid exchanges alter the properties of the receptors and channels. Consistently, changes in editing patterns are frequently found associated with diseases of the CNS. In this review we describe the mechanisms of RNA editing and focus on target mRNAs of editing that are functionally relevant to normal and aberrant CNS activity.

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

“…RNA editing profoundly affects gene expression and cellular function, and alterations in editing have been implicated in cancer and neurological disease (11,34,65,66). However, expression levels of the ADAR enzymes do not always correlate with the extent of editing (67,68).…”

“…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).…”

“…RNA editing are often associated with diseases of the central nervous system including neurodegenerative diseases and astrocytomas (11,34); in fact, one commonality between the neurological disease amyotrophic lateral sclerosis (ALS) and glioblastoma (also referred to as grade IV astrocytoma) is reduced editing of one particular transcript, GRIA2 (9,35).…”

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

“…The majority of protein recoding editing events have been identified in the nervous system, where the editing-induced amino acid exchanges modulate the activity of the encoded proteins [8]. Outside the nervous system, one of the most prominent editing-induced recoding events occurs in filamins.…”