title: snoRNA U17 regulates cellular cholesterol trafficking.
abstract: 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.
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jinn
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Brandis
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Aileen
authors.initials: A
authors.lastname: Ren
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Chacko
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Dudley-Rucker
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gale
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Rohini
authors.initials: R
authors.lastname: Sidhu
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Hideji
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Brett N
authors.initials: BN
authors.lastname: Olsen
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Jean E
authors.initials: JE
authors.lastname: Schaffer
authors.affiliation: Diabetic Cardiovascular Disease Center and Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: dory@wustl.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Ory
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D016466:CHO Cells; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D041681:NIH 3T3 Cells; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005136:Eye Proteins; C509731:MGARP protein, mouse; D024101:Mitochondrial Proteins; D020537:RNA, Small Nucleolar; D002784:Cholesterol