Serotonin receptor 2c is very important for the functioning of the central nervous system (CNS), as it participates in the control of eating, mood, behavior, motor and cognitive processes. Its activity is governed by two posttrancriptional modifications – deamination of adenosines to inosines (A-to-I RNA editing) and alternative splicing of exons. Both occur on the pre-mRNA encoding 5-HT2C receptor and have significant effect on the functioning of the receptor. A-to-I editing at five closely spaced adenosines (A, B, C, D, E) on alternative exon Vb is catalysed by enzymes ADAR (Adenosine Deaminases Acting on RNA), and can alter the codons and change amino acid sequence of the second intracellular loop through which receptor couples to proteins G. Small nucleolar RNA (snoRNA) SNORD115, which contains a phylogenetically conserved 18-nucleotide antisense element with perfect complementarity to the alternative exon Vb of 5ht2c primary trancript, finely regulates receptor's functionality. SNORD115 regulates alternative splicing of exons by binding to silencing element at the proximal splice site, which promotes exon Vb inclusion and the formation of fully functional long receptor isoform. It is also assumed that SNORD115 blocks A-to I editing of the 5ht2c trancript, thereby increasing the signaling ability of the receptor. SNORD115@ gene cluster is located on human chromosome 15q11-13. Deletion of paternally imprinted locus in that region results in Prader-Willi syndrome, a rare genetic disorder characterized by psychiatric, developmental and behavioural problems. The expression of ADAR and SNORD115 genes can be influenced by environmental and genetic factors, as well as drug treatment and exposure to stress in youth and adulthood. We used quantitative polymerase chain reaction (qPCR) to study the effects of genetics (strain) and environment (enriched and standard) on the expression of SNORD115 and ADAR genes in the prefrontal cortex of two mice strains, BALB/c and C57BL/6, which differ in serotonin levels in the CNS. In addition, we used next generation sequencing to analyse the expression and frequency of individual mRNA isoforms and the extent of adenosine deamination at all five positions. We have found that neither genetics nor choice of environment have significant influence on the expression of selected genes in the mouse brain prefrontal cortex. Their influence on the expression of individual edited isoforms and the extent of editing at individual positions, at least in the 4 week time window, is negligible.
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