Regulation of Neuronal Function by RNA editing; physiological role(s) of CGRP
Ronald B. Emeson
Associate Professor of Pharmacology and Molecular Physiology & Biophysics
460 Preston Research Building
Our laboratory is examining the molecular mechanisms involved in the editing of numerous RNA transcripts in the mammalian central nervous system. RNA editing is a post-transcriptional modification in which specific adenosine residues in pre-messenger RNAs are converted to inosine moieties (A-to-I editing) via the actions of double-stranded RNA-specific adenosine deaminases (ADARs). As a result of these deamination events, the coding potential of RNAs can be subtly altered to change as little as a single amino acid residue in resultant proteins.
In the case of glutamate-gated ion channels, RNA editing can dramatically alter both the ion permeation and electrophysiologic properties of these ionotropic receptors. Since glutamate-gated channels are critically involved in processes of excitatory neurotransmission, slight alterations in RNA editing patterns have profound effects upon the normal neurophysiology of the brain.
RNA editing events within the 2C-subtype of serotonin receptor (5HT2CR) can modulate the efficacy by which this seven transmembrane-spanning receptor can couple to its specific intracellular signaling pathways. Since this serotonin receptor has been implicated in a number of neuropsychiatric disease states, including anxiety, depression and schizophrenia, aberrant RNA editing patterns may play an important role in the etiology of these disorders. Mutant mice solely expressing the non-edited form of the 5HT2CR demonstrate deficits in maternal behavior, while animals solely expressing the fully-edited isoform have a number of phenotypic alterations characteristic of human Prader-Willi syndrome. Current research efforts in the laboratory focus upon the regulation of ADAR expression, the role of RNA editing in central feeding behavior and further analyses of the phenotypic consequences resulting from changes in the editing of 5HT2CR transcripts.