snoRNA U17 Regulates Cellular Cholesterol Trafficking

Jinn, Sarah; Brandis, Katrina; Ren, Aileen; Chacko, Anita; Dudley-Rucker, Nicole; Gale, Sarah E.; Sidhu, Rohini; Fujiwara, Hideji; Jiang, Hui; Olsen, Brett N.; Schaffer, Jean E.; Ory, Daniel S.

doi:10.1016/j.cmet.2015.04.010

Cited by 55 publications

(32 citation statements)

References 50 publications

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“…Intriguingly, this hypothesis is favored by recent studies that established an emerging role of snoRNAs in specific metabolic functions. A striking example is that of U17, a dyskerin binding snoRNA involved in intracellular cholesterol trafficking . Worth noting, proper sorting and trafficking within endosomal vesicles is necessary to maintain cellular homeostasis and to perform both ubiquitous and cell type‐specific functions.…”

Section: Discussionmentioning

confidence: 99%

A new role for human dyskerin in vesicular trafficking

et al. 2017

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Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X‐linked dyskeratosis congenita and Hoyeraal‐Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras‐related protein Rab‐5A/Rab11 trafficking. These effects arise in different cell lines well before the onset of telomere shortening, which is widely considered the main cause of dyskerin‐related diseases. Given that vesicular trafficking affects many homeostatic and differentiative processes, these findings add novel insights into the molecular mechanisms underlining the pleiotropic manifestation of the dyskerin loss‐of‐function phenotype.

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Section: Discussionmentioning

confidence: 99%

A new role for human dyskerin in vesicular trafficking

et al. 2017

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“…Mitochondria associated membranes are also rich in cholesterol and in the simple sphingolipid ceramide (106). An outer mitochondrial membrane adaptor protein, hypoxia-upregulated mitochondrial movement regulator (HUMMR), increases the ER-mitochondria MCSs to facilitate cholesterol flux to mitochondria (107). Interestingly, studies in a mouse model for Alzheimer's disease (AD) showed that, in the early stage of AD development, synaptic mitochondria exhibit significant functional deficits; the degree of deficits correlates positively with amyloid- (A) peptide accumulation (108).…”

Section: The Three Cholesterol Trafficking Routes In a Mammalian Cellmentioning

confidence: 99%

Cellular cholesterol homeostasis and Alzheimer's disease

Chang

Yamauchi

Hasan

et al. 2017

Journal of Lipid Research

121

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Alzheimer's disease (AD) is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid-β (Aβ) peptides (especially Aβ1-42) and neurofibrillary tangles, composed of hyperphosphorylated tau and accompanied by chronic neuroinflammation. Aβ peptides are derived from the amyloid precursor protein (APP). The oligomeric form of Aβ peptides is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques. ApoE is the major apolipoprotein of the lipoprotein(s) present in the CNS. ApoE has three alleles, of which the allele constitutes the major risk factor for late-onset AD. Here we describe the complex relationship between ApoE4, oligomeric Aβ peptides, and cholesterol homeostasis. The review consists of four parts:) key elements involved in cellular cholesterol metabolism and regulation; ) key elements involved in intracellular cholesterol trafficking;) links between ApoE4, Aβ peptides, and disturbance of cholesterol homeostasis in the CNS; ) potential lipid-based therapeutic targets to treat AD. At the end, we recommend several research topics that we believe would help in better understanding the connection between cholesterol and AD for further investigations.

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“…In the same way, Brandis et al [52] has shown that the box C/D snoRNA U60 regulates intracellular cholesterol trafficking between the plasma membrane and the endoplasmic reticulum. Similarly, the snoRNA U17 regulates the cellular cholesterol trafficking through the hypoxia-upregulated mitochondrial regulator (HUMMR) by acting on its target mRNA [53]. Here, the modification of the level of the h-jou, either its overexpression or its depletion leads to a strong deregulation of metabolic pathways as revealed by the KEGG analysis (about 400 genes).…”

Section: Discussionmentioning

confidence: 99%

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

El-Khoury

Bignon

Martin

2020

Preprint

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Small nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan.Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome.We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

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snoRNA U17 Regulates Cellular Cholesterol Trafficking

Cited by 55 publications

References 50 publications

A new role for human dyskerin in vesicular trafficking

A new role for human dyskerin in vesicular trafficking

Cellular cholesterol homeostasis and Alzheimer's disease

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

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