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Cited by 29RNA regulation and diseaseRNA Research and SplicingRNA and protein synthesis mechanisms

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

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Raabe, Carsten A., Voss, Reinhard, Kummerfeld, Delf-Magnus, Brosius, Juergen, Galiveti, Chenna R., Wolters, Anna, Seggewiss, Jochen, Huge, Andreas +2 more·2019·Scientific Reports
DOI 10.1038/s41598-019-39940-6PMC PMC6414643
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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.

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Cited by

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Authors
Raabe, C. A., Voss, R., Kummerfeld, D.-M., Brosius, J., Galiveti, C. R., Wolters, A., Seggewiss, J., Huge, A., Skryabin, B. V., & Rozhdestvensky, T. S.
Affiliations
  • University of Münster (DE)
  • University Hospital Münster (DE)
Corresponding author
  • Skryabin, Boris V.
  • Rozhdestvensky, Timofey S.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-03-12
Volume
9
Issue
1
Pages
4300-4300
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-39940-6
PMC
PMC6414643
OpenAlex
W2922449218
Cited by
29
References
2
Citations by year
2026: 2 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 1
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (SK259/2-1, RO5622/1-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
5-HT2C receptor, serotonin receptors, A-to-I RNA editing, alternative splicing, small nucleolar RNA, choroid plexus, ADAR, post-transcriptional processing, double-stranded RNA
MeSH terms
Animals, Choroid Plexus, Female, Genotype, Male, Mice, Mutant Strains, RNA Splicing, RNA Editing, Alternative Splicing, RNA, Small Nucleolar, Mice

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