Characterization of RNASET2, the first human member of the Rh/T2/S family of glycoproteins

Campomenosi, Paola; Salis, Silvia; Lindqvist, Christer; Mariani, Davide; Nordström, Tommy; Acquati, Francesco; Taramelli, Roberto

doi:10.1016/j.abb.2006.02.022

Cited by 60 publications

(69 citation statements)

References 27 publications

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“…However, modification by mannose-6-phosphate residues, subcellular fraction studies, and an acidic pH optimum indicate that RNASET2 resides in the lysosomes of mammalian cells, where selectivity of RNA degradation may be maintained by both the physical and chemical environment. 30,43 In contrast to the yeast Rny1p, which localizes to the vacuole but is released to the cytoplasm on oxidative stress, 27 we did not detect mammalian RNASET2 in the soluble, cytoplasmic fraction of CHO cells following lipotoxic or oxidative stress (not shown). Rather, RNASET2 likely functions in these pathways within the lysosomal lumen, where it may encounter RNA substrates delivered by lipidinduced microautophagy, mitophagy and ribophagy.…”

Section: Discussionmentioning

confidence: 64%

“…A catalytically inactive (CI) murine RNASET2 construct was generated through site-directed mutagenesis of two of the three catalytic histidines. 29,30 Transient overexpression of both WT and CI murine constructs in CHO cells produced glycosylated, mature RNASET2 protein, recognized by an antiserum specific for the murine protein (Figure 3a). Zymography confirmed that only the WT construct had functional RNase activity at the permissive pH of 5.…”

Section: Resultsmentioning

confidence: 99%

“…44,45 RNASET2 may be targeted directly to lysosomes by trafficking from the Golgi to the endosomal system; 46 however, evidence that RNASET2 is secreted and subsequently taken up by target cells raises the possibility that this enzyme may also traffic to the lysosome indirectly from the plasma membrane following endocytosis. 30,39 Prior studies have established roles for RNASET2 in tumor progression, vitiligo, and neurodevelopmental development abnormalities. 32,39,47 Our study provides new insights into the function of this lysosomal enzyme as a regulator of pathophysiological oxidative stress responses and adds to a growing body of evidence that the lysosome and its components are essential for integrating a wide array of metabolic stimuli into cell fate decisions.…”

Section: Discussionmentioning

confidence: 99%

“…Zymography was performed as described. 30 Detection of ROS. Following treatments as indicated, cells were rinsed with PBS and incubated at 37°C in the dark with PBS containing 0.5 mM MgCl 2 , 0.92 mM CaCl 2 , and either 3 μM DCF for 1 h or 10 μM DHE for 15 min.…”

Section: Discussionmentioning

confidence: 99%

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RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

et al. 2015

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RNASET2 is a ubiquitously expressed acidic ribonuclease that has been implicated in diverse pathophysiological processes including tumorigeneis, vitiligo, asthenozoospermia, and neurodegeneration. Prior studies indicate that RNASET2 is induced in response to oxidative stress and that overexpression of RNASET2 sensitizes cells to reactive oxygen species (ROS)-induced cell death through a mechanism that is independent of catalytic activity. Herein, we report a loss-of-function genetic screen that identified RNASET2 as an essential gene for lipotoxic cell death. Haploinsufficiency of RNASET2 confers increased antioxidant capacity and generalized resistance to oxidative stress-mediated cell death in cultured cells. This function is critically dependent on catalytic activity. Furthermore, knockdown of RNASET2 in the Drosophila fat body confers increased survival in the setting of oxidative stress inducers. Together, these findings demonstrate that RNASET2 regulates antioxidant tone and is required for physiological ROS responses.

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Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

et al. 2015

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“…RNase T2 enzymes are acidic RNases found almost ubiquitously in eukaryotes. This family of RNases is hypothesized to have an essential role leading to its conservation and has been shown to be involved in transfer RNA (tRNA) and rRNA degradation ) Mutation of both the zebrafish and human RNase T2 result in accumulation of rRNA in the lysosome , and in each organism RNase T2 is normally localized to the lysosome (Campomenosi et al 2006;. An Arabidopsis RNase T2 is required for normal turnover of rRNA and is a likely candidate for being part of a ribophagy-like process in plants.…”

Section: The Selective Autophagy Of Ribosomesmentioning

confidence: 99%

Analysis of the role of RNS2 and autophagy in the turnover of ribosomal RNA in Arabidopsis thaliana

Floyd

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HIF2α‐induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma

et al. 2023

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Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF‐2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.

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Characterization of RNASET2, the first human member of the Rh/T2/S family of glycoproteins

Cited by 60 publications

References 27 publications

RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

Analysis of the role of RNS2 and autophagy in the turnover of ribosomal RNA in Arabidopsis thaliana

HIF2α‐induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma

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