Cell Metabolism
Volume 21, Issue 6, 2 June 2015, Pages 855-867
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Article
snoRNA U17 Regulates Cellular Cholesterol Trafficking

https://doi.org/10.1016/j.cmet.2015.04.010Get rights and content
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Highlights

  • Haploinsufficiency of U17 snoRNA alters intracellular cholesterol trafficking

  • HUMMR acts downstream of U17 snoRNA to regulate cholesterol delivery to mitochondria

  • U17 snoRNA and HUMMR developmentally regulate steroidogenesis in vivo

Summary

Cholesterol is required for the growth and viability of mammalian cells and is an obligate precursor for steroid hormone synthesis. Using a loss-of-function screen for mutants with defects in intracellular cholesterol trafficking, a Chinese hamster ovary cell mutant with haploinsufficiency of the U17 snoRNA was isolated. U17 is an H/ACA orphan snoRNA, for which a function other than ribosomal processing has not previously been identified. Through expression profiling, we identified hypoxia-upregulated mitochondrial movement regulator (HUMMR) mRNA as a target that is negatively regulated by U17 snoRNA. Upregulation of HUMMR in U17 snoRNA-deficient cells promoted the formation of ER-mitochondrial contacts, decreasing esterification of cholesterol and facilitating cholesterol trafficking to mitochondria. U17 snoRNA and HUMMR regulate mitochondrial synthesis of steroids in vivo and are developmentally regulated in steroidogenic tissues, suggesting that the U17 snoRNA-HUMMR pathway may serve a previously unrecognized, physiological role in gonadal tissue maturation.

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