Abstract
SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated Snord115 knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in Htr2c RNA editing profiles, while Htr2c alternative RNA splicing was unchanged. These subtle changes, whose functional relevance remains uncertain, were not accompanied by any discernible defects in anxio-depressive-like phenotypes. Energy balance and eating behavior were also normal, even after exposure to high-fat diet. Our study raises questions concerning the physiological role of SNORD115, notably its involvement in behavioural disturbance associated with PWS.
Highlights
Box C/D small nucleolar RNAs (SNORDs) represent a well-defined family of small non-coding RNAs that exert their regulatory functions via antisense-based mechanisms
Because Snord115 genes are only expressed from the paternal allele, ~50% of Snord115-deficient mice are expected to be obtained in the progeny after crossing wild-type females with heterozygous males
We aimed at testing, for the first time and at the organism level, the hypothesis according to which SNORD115 regulates the processing of HTR2C pre-mRNA and, in doing so, influences HTR2C-mediated brain functions
Summary
Box C/D small nucleolar RNAs (SNORDs) represent a well-defined family of small non-coding RNAs that exert their regulatory functions via antisense-based mechanisms. The vast majority forms base-pairing interactions with ribosomal RNA (rRNA) precursor, spliceosomal U6 snRNA or tRNA and, in doing so, they guide sequence-specific ribose methylations (Cavailleet al., 1996; Ganot et al, 1999; Kiss-Laszloet al., 1996; Vitali and Kiss, 2019) or, in rare cases, base acetylation (Sharma et al, 2017). By acting as RNA folding chaperones, a few are specialized to facilitate. Nucleoli contain orphan SNORDs lacking conserved antisense elements against canonical RNA targets, raising the possibility that some may interact with uncharacterized targets, possibly including mRNAs (Bratkovicet al., 2020)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
