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Sci Rep. 2019 Mar 12;9(1):4300. doi: 10.1038/s41598-019-39940-6.

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

Author information

1
Institute of Experimental Pathology (ZMBE), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany.
2
Institute of Medical Biochemistry (ZMBE), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany.
3
Laukamp 12, D-48161, Muenster, Germany.
4
Medical Faculty, Core Facility Transgenic animal and genetic engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany.
5
Brandenburg Medical School (MHB), Fehrbellinerstr. 38, D-16816, Neuruppin, Germany.
6
Institute of Human Genetics, University Hospital Muenster, Vesaliusweg 12-14, D-48149, Muenster, Germany.
7
Medical Faculty, Core Facility Genomik, University of Muenster, Albert-Schweitzer-Campus 1, D3, Domagkstrasse 3, D-48149, Muenster, Germany.
8
Medical Faculty, Core Facility Transgenic animal and genetic engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany. skryabi@uni-muenster.de.
9
Medical Faculty, Core Facility Transgenic animal and genetic engineering Models (TRAM), University of Muenster, Von-Esmarch-Str. 56, D-48149, Muenster, Germany. rozhdest@uni-muenster.de.

Abstract

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.

PMID:
30862860
DOI:
10.1038/s41598-019-39940-6
Free PMC Article

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