Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

Lee, Jiyeon; Harris, Alexis N.; Holley, Christopher L.; Mahadevan, Jana; Pyles, Kelly D.; Lavagnino, Zeno; Scherrer, David E.; Fujiwara, Hideji; Sidhu, Rohini; Zhang, Jessie; Huang, Stanley Ching-Cheng; Piston, David W.; Remedi, Marı́a S.; Urano, Fumihiko; Ory, Daniel S.; Schaffer, Jean E.

doi:10.1172/jci88069

Cited by 75 publications

(66 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As well as lipotoxicity, SNORDs participate in other processes, including glucose tolerance and cholesterol trafficking. Mice with a specific knock down of SNORD32A, 33, 34 and 35a that did not alter expression of the protein encoded by the hosting genes RPL13A exhibited an increased systemic glucose tolerance and glucose-mediated insulin secretion [58]. Thus lack of these SNORDs promotes the clearance of circulating glucose possibly caused by decreased production of reactive oxygen species [58].…”

Section: Diseases Caused By Snorna Loss Indicate New Functionsmentioning

confidence: 99%

“…Mice with a specific knock down of SNORD32A, 33, 34 and 35a that did not alter expression of the protein encoded by the hosting genes RPL13A exhibited an increased systemic glucose tolerance and glucose-mediated insulin secretion [58]. Thus lack of these SNORDs promotes the clearance of circulating glucose possibly caused by decreased production of reactive oxygen species [58]. Using a similar screening system SNORD60 was found to act in intracellular cholesterol trafficking, which is independent of its suggested function in ribosomal RNA methylation [59].…”

Section: Diseases Caused By Snorna Loss Indicate New Functionsmentioning

confidence: 99%

“…Novel SNORD functions were indicated by genome wide RNA profiling of diseases that showed deregulation of numerous SNORDs, but gave little mechanistic insights [70–73] [65] [69]. A few SNORDs were analyzed in great detail using mostly transfection studies [74–76] and even transgenic mice [58, 77, 78], which gave insight in to physiological processes. Mechanistical insight has come from detailed biochemical analysis [79] and the development of new techniques identifying RNA:RNA interactions [80].…”

Section: Snords Form Non-methylating Ribonucleic Protein Complexes Anmentioning

confidence: 99%

See 2 more Smart Citations

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

et al. 2017

View full text Add to dashboard Cite

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding RNAs that have been long known to perform 2′-O-methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non-methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under-appreciated. The action of SNORDs in non-methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader-Willi syndrome.

show abstract

Section: Diseases Caused By Snorna Loss Indicate New Functionsmentioning

confidence: 99%

Section: Diseases Caused By Snorna Loss Indicate New Functionsmentioning

confidence: 99%

Section: Snords Form Non-methylating Ribonucleic Protein Complexes Anmentioning

confidence: 99%

See 1 more Smart Citation

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Ribose methylated bases are also found at mRNA caps and are involved in host pathogen responses (Daffis et al 2010;Rimbach et al 2015). Recent evidence indicates that in addition to being associated with the 5 ′ cap, mRNAs might potentially possess internal 2 ′ -O-methylated sites (Lee et al 2016).…”

Section: Introductionmentioning

confidence: 99%

High-throughput and site-specific identification of 2′-O-methylation sites using ribose oxidation sequencing (RibOxi-seq)

Zhu

Pirnie

Carmichael

2017

RNA

View full text Add to dashboard Cite

Ribose methylation (2 ′ ′ ′ ′ ′ -O-methylation, 2 ′ ′ ′ ′ ′ -OMe) occurs at high frequencies in rRNAs and other small RNAs and is carried out using a shared mechanism across eukaryotes and archaea. As RNA modifications are important for ribosome maturation, and alterations in these modifications are associated with cellular defects and diseases, it is important to characterize the landscape of 2 ′ ′ ′ ′ ′ -Omethylation. Here we report the development of a highly sensitive and accurate method for ribose methylation detection using next-generation sequencing. A key feature of this method is the generation of RNA fragments with random 3 ′ ′ ′ ′ ′ -ends, followed by periodate oxidation of all molecules terminating in 2 ′ ′ ′ ′ ′ ,3 ′ ′ ′ ′ ′ -OH groups. This allows only RNAs harboring 2 ′ ′ ′ ′ ′ -OMe groups at their 3 ′ ′ ′ ′ ′ -ends to be sequenced. Although currently requiring microgram amounts of starting material, this method is robust for the analysis of rRNAs even at low sequencing depth.

show abstract

“…In addition to the well-known canonical function of the snoRNA in various RNA modifications, more recently, some snoRNAs have been involved in stress response and metabolic homeostasis. For examples, the snoRNA U32a, U33 and U35a are mediators of oxidative stress [50], while the same snoRNAs seem also to regulate the systemic glucose metabolism [51]. 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.…”

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

View full text Add to dashboard Cite

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.

show abstract

Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

Cited by 75 publications

References 58 publications

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

High-throughput and site-specific identification of 2′-O-methylation sites using ribose oxidation sequencing (RibOxi-seq)

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

Contact Info

Product

Resources

About