The roles of phospholipase C activation and alternative ADAR1 and ADAR2 pre-mRNA splicing in modulating serotonin 2C-receptor editing in vivo.

RNA
Claudia SchmaussLauren P Shapiro

Abstract

The serotonin 2C receptor (5-HT2CR), a Gq-protein-coupled neurotransmitter receptor, exists in multiple isoforms that result from RNA editing of five exonic adenosines that are converted to inosines. In the adult brain, editing of 5-HT2C pre-mRNA exhibits remarkable plasticity in response to environmental and neurochemical stimuli. Here, we investigated two potential mechanisms underlying these plastic changes in adult 5-HT2CR editing phenotypes in vivo: activation of phospholipase C (PLC) and alternative splicing of pre-mRNA encoding the editing enzymes ADAR1 and ADAR2. Studies on two inbred strains of mice (C57Bl/6 and Balb/c) revealed that sustained stimulation of PLC--a downstream effector of activated G alpha q protein--increased editing of forebrain neocortical 5-HT2C pre-mRNA at two sites known to be targeted by ADAR2. Moreover, changes in relative expression of the alternatively spliced "a" and "b" mRNA isoforms of ADAR1 and ADAR2 also correlate with changes in 5-HT2CR editing. The site-specific changes in 5-HT2CR editing detected in mice with different "a" over "b" ADAR mRNA isoform ratios only partially overlap with those evoked by sustained PLC activation and are best explained by the increased editing efficiency of ...Continue Reading

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Citations

Feb 16, 2011·Behavioral Neuroscience·Mukti Mehta, Claudia Schmauss
Nov 3, 2012·BMC Neuroscience·Prashant MandelaRichard E Mains
Nov 25, 2011·Molecular Neurobiology·Cesare OrlandiSergio Barlati
May 3, 2014·Scientific Reports·Claudia SchmaussLiorimar Ramos Medina
Jan 18, 2013·RNA Biology·Takashi ShimokawaPeter G Zaphiropoulos
Nov 12, 2015·Biology of Sex Differences·Aaron BlockKatheleen J Gardiner
Jul 1, 2017·Human Genetics·Stefan StammRonald B Emeson
Jan 8, 2021·Behavioural Brain Research·Xiaonan ZhangShengming Yin

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