Ectopic expression of Snord115 in choroid plexus interferes with editing but not splicing of 5-Ht2c receptor pre-mRNA in mice

• Published in: Scientific reports Vol. 9; no. 1; p. 4300
• Main Authors: Raabe, Carsten A., Voss, Reinhard, Kummerfeld, Delf-Magnus, Brosius, Juergen, Galiveti, Chenna R., Wolters, Anna, Seggewiss, Jochen, Huge, Andreas, Skryabin, Boris V., Rozhdestvensky, Timofey S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2019; Nature Publishing Group
• Subjects: 38/71; 38/91; 45/41; 45/77; 631/208/199; 631/337/384/521; 64/110; 64/60; Alternative splicing; Alternative Splicing - genetics; Alternative Splicing - physiology; Animal models; Animals; Autism; Choroid plexus; Choroid Plexus - metabolism; Complementarity; Ectopic expression; Editing; Female; Genotype; Humanities and Social Sciences; Male; Mental disorders; Mice; Mice, Mutant Strains; mRNA; multidisciplinary; Neurodegenerative diseases; Nucleoli; Post-transcription; RNA Editing - genetics; RNA Editing - physiology; RNA processing; RNA Splicing - genetics; RNA Splicing - physiology; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - metabolism; Science; Science (multidisciplinary); Serotonin S2 receptors; Sleep; snoRNA; Statistical analysis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39940-6

Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulated via alternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA. For almost two decades this putative guide element of Snord115 has wandered like a ghost through the literature in attempts to elucidate the biological significance of this complementarity. In mice, Snord115 is expressed in neurons and absent in the choroid plexus where, in contrast, 5-Ht2cr mRNA is highly abundant. Here we report the analysis of 5-Ht2cr pre-mRNA posttranscriptional processing via RNA deep sequencing in a mouse model that ectopically expresses Snord115 in the choroid plexus. In contrast to previous reports, our analysis demonstrated that Snord115 does not control alternative splicing of 5-Ht2cr pre-mRNA in vivo . We identified a modest, yet statistically significant reduction of 5-Ht2cr pre-mRNA A to I editing at the major A, B, C and D sites. We suggest that Snord115 and exon Vb of 5Ht2cr pre-mRNA form a double-stranded structure that is subject to ADAR-mediated A to I editing. To the best of our knowledge, this is the first comprehensive Snord115 gain-of-function analysis based on in vivo mouse models.