Reassessment of the involvement of Snord115 in the serotonin 2c receptor pathway in a genetically relevant mouse model

Elife. 2020 Oct 5;9:e60862. doi: 10.7554/eLife.60862.

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.

Keywords: RNA editing; alternative RNA splicing; chromosomes; eating disorder; gene expression; mouse; prader-willi syndrome; serotonin 2c receptor; snoRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • CRISPR-Cas Systems
  • Diet, High-Fat
  • Emotions*
  • Feeding Behavior / physiology*
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*
  • Receptor, Serotonin, 5-HT2C / genetics
  • Receptor, Serotonin, 5-HT2C / metabolism*

Substances

  • RNA, Messenger
  • RNA, Small Nucleolar
  • Receptor, Serotonin, 5-HT2C

Associated data

  • GEO/GSE145159