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2015 ; 21
(6
): 855-67
Nephropedia Template TP
Jinn S
; Brandis KA
; Ren A
; Chacko A
; Dudley-Rucker N
; Gale SE
; Sidhu R
; Fujiwara H
; Jiang H
; Olsen BN
; Schaffer JE
; Ory DS
Cell Metab
2015[Jun]; 21
(6
): 855-67
PMID25980348
show ga
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.