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. 2012 Jul 9:6:99.
doi: 10.3389/fnins.2012.00099. eCollection 2012.

Transcript diversification in the nervous system: a to I RNA editing in CNS function and disease development

Aamira Tariq  1 , Michael F Jantsch
Affiliations

Transcript diversification in the nervous system: a to I RNA editing in CNS function and disease development

Aamira Tariq et al. Front Neurosci. .

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.

Keywords: RNA editing; RNA modification; calcium channel; glutamate receptor; inosine; potassium channel; serotonin receptor.

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Figures

Figure 1
Figure 1
Impact of editing on selected neuronal receptors and proteins. Shown are several receptors and channels in their unedited (black) and edited (E, in pink) versions. Editing at the Q/R site of ionotropic glutamate receptor GluA2 subunit decreases Ca2+permeability and endoplasmic reticulum exit efficiency. Membrane trafficking of the GABAA receptor is reduced by editing of I to M in the alpha3 subunit. Editing of the serotonin 5-HT2c receptor converts the amino acids I-N-I to V-S-V or V-N-V. This reduces G-protein coupling in the receptor. The editing-induced I to V exchange in Kv1.1 (I/V) alters the interaction with Kv β1.1 (see Figure 3 for detail). Editing of the IQ motiv in Cav1.3 to MR abolishes calmodulin binding. Filamin alpha (FLNa) is edited in a region that is known to interact with metabotropic glutamate receptor mGlu7b and some of its relatives.
Figure 2
Figure 2
Topography of the neuronal channels containing editing sites Ionotropic glutamate receptor, GABAA receptor subunit α3, Kv1.1, Cav1.3, and 5-HT2c receptors are shown. The relative position of the editing sites within these receptors are highlighted. Consequences of editing are indicated.
Figure 3
Figure 3
Regulation of the Kv1.1 channel by Kv β1.1 Kv β1.1 has an inactivation gate which interacts with the unedited (I) form of the Kv1.1 receptor. Editing of Kv1.1 changes the isoleucine to valine (V). This reduces the affinity for Kv β1.1 and enhances recovery from inactivation. Figure adapted from (Bezanilla, 2004).
Figure 4
Figure 4
Cav1.3 and calmodulin interaction. Calmodulin binds to Cav1.3 without calcium as apoCaM at the IQ motif. Calmodulin binds to calcium through its N-terminal and C-terminal loop and mediates calcium dependent inhibition (CDI). Editing modifies IQ to MR and inhibits calmodulin binding. Intracellular calcium increases in the absence of CDI.
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