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Peer-reviewedCC BY 4.0Life Science Alliance

Diacylglycerol kinase kappa is a target of the Prader–Willi syndrome gene SNORD116

  • Yiying Zhang1
  • Kaiying Guo1
  • Gabriel F Batzli1
  • Haoquan Zhao2
  • Lisa C Burnett3
  • Charles A LeDuc4
  • George Stratigopoulos5,6
  • Daniel G Carolan1
  • Claudia A Doege7
  • Yufeng Shen2
  • Rudolph L Leibel1
7 affiliations
  1. 1Department of Pediatrics, Division of Molecular Genetics, Columbia University Irving Medical Center, New York, NY, USA
  2. 2Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
  3. 3Foundation for Prader-Willi Research, Covina, CA, USA
  4. 4Department of Pediatrics, Division of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
  5. 5Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA
  6. 6Brain Sciences Center, Minneapolis VA Health Care System, Minneapolis, MN, USA
  7. 7Department of Pathology and Cell Biology, Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, NY, USA
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Abstract

SNORD116 is a small nucleolar RNA deficient in Prader–Willi syndrome individuals. The mechanisms by which SNORD116 conveys its effects are unknown. Here, transcriptomic analysis showed that diacylglycerol kinase kappa (Dgkk) expression was elevated in the hypothalamus of Snord116-deficient mice. In silico analyses predicted a strong RNA:RNA interaction between Snord116 and Dgkk mRNA that is fully conserved in mouse and human. In vitro experiments in human cellular models demonstrated that SNORD116 mediates 2′-O-methylation of DGKK mRNA and regulates DGKK mRNA and protein expression. In Snord116-deficient mouse neurons, increased Dgkk expression was associated with attenuated diacylglycerol-mediated activation of ERK and PKC, critical elements in neuronal signaling cascades. In mice, brain Dgkk expression peaks during late embryonic and early postnatal periods, coinciding with peak rates of neurogenesis; its expression in adults is restricted mainly to brain regions implicated in Prader–Willi syndrome pathophysiology, including the arcuate nucleus of the hypothalamus. Fasting acutely decreased hypothalamic Dgkk expression in wild-type mice. Increased Dgkk expression in Snord116-deficient mice could reflect derangements in this pathway that affects both brain development and cell-specific functions.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026diacylglycerol,
  title = {{Diacylglycerol kinase kappa is a target of the Prader–Willi syndrome gene SNORD116}},
  author = {Yiying Zhang and Kaiying Guo and Gabriel F Batzli and Haoquan Zhao and Lisa C Burnett and Charles A LeDuc and George Stratigopoulos and Daniel G Carolan and Claudia A Doege and Yufeng Shen and Rudolph L Leibel},
  journal = {Life Science Alliance},
  year = {2026},
  month = nov,
  doi = {10.26508/lsa.202603723},
  url = {https://doi.org/10.26508/lsa.202603723},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Diacylglycerol kinase kappa is a target of the Prader–Willi syndrome gene SNORD116
AU  - Yiying Zhang
AU  - Kaiying Guo
AU  - Gabriel F Batzli
AU  - Haoquan Zhao
AU  - Lisa C Burnett
AU  - Charles A LeDuc
AU  - George Stratigopoulos
AU  - Daniel G Carolan
AU  - Claudia A Doege
AU  - Yufeng Shen
AU  - Rudolph L Leibel
PY  - 2026
DA  - 2026/11/04
JO  - Life Science Alliance
DO  - 10.26508/lsa.202603723
UR  - https://doi.org/10.26508/lsa.202603723
AB  - SNORD116 is a small nucleolar RNA deficient in Prader–Willi syndrome individuals. The mechanisms by which SNORD116 conveys its effects are unknown. Here, transcriptomic analysis showed that diacylglycerol kinase kappa (Dgkk) expression was elevated in the hypothalamus of Snord116-deficient mice. In silico analyses predicted a strong RNA:RNA interaction between Snord116 and Dgkk mRNA that is fully conserved in mouse and human. In vitro experiments in human cellular models demonstrated that SNORD116 mediates 2′-O-methylation of DGKK mRNA and regulates DGKK mRNA and protein expression. In Snord116-deficient mouse neurons, increased Dgkk expression was associated with attenuated diacylglycerol-mediated activation of ERK and PKC, critical elements in neuronal signaling cascades. In mice, brain Dgkk expression peaks during late embryonic and early postnatal periods, coinciding with peak rates of neurogenesis; its expression in adults is restricted mainly to brain regions implicated in Prader–Willi syndrome pathophysiology, including the arcuate nucleus of the hypothalamus. Fasting acutely decreased hypothalamic Dgkk expression in wild-type mice. Increased Dgkk expression in Snord116-deficient mice could reflect derangements in this pathway that affects both brain development and cell-specific functions.
SN  - 2575-1077
ER  -