Human sphingomyelin synthase 1 gene (SMS1): Organization, multiple mRNA splice variants and expression in adult tissues

Rozhkova, A. V.; Дмитриева, В. Г.; Zhapparova, Olga; Sudarkina, Olga Yu.; Nadezhdina, E. S.; Limborska, Svetlana A.; Dergunova, Lyudmila V.

doi:10.1016/j.gene.2011.04.010

Cited by 19 publications

(6 citation statements)

References 56 publications

(65 reference statements)

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“…This behavior has previously been reported for SMS1 [23], reflecting the high post-transcriptional regulation these enzymes undergo. SMS1 is a complex gene with several splicing forms [43] capable of generating circular and linear RNAs [44,45]. Furthermore, it contains recursive exons and participates in a multi-step splicing process involved in the generation of a wide array of RNAs, some of them with unknown roles [46].…”

Section: Discussionmentioning

confidence: 99%

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Fernández‐García

Rosselló

Rodríguez-Lorca

et al. 2019

Cancers

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Background: 2-Hydroxyoleic acid (2OHOA) is particularly active against glioblastoma multiforme (GBM) and successfully finished a phase I/IIA trial in patients with glioma and other advanced solid tumors. However, its mechanism of action is not fully known. Methods: The relationship between SMS1 and SMS2 expressions (mRNA) and overall survival in 329 glioma patients was investigated, and so was the correlation between SMS expression and 2OHOA’s efficacy. The opposing role of SMS isoforms in 2OHOA’s mechanism of action and in GBM cell growth, differentiation and death, was studied overexpressing or silencing them in human GBM cells. Results: Patients with high-SMS1 plus low-SMS2 expression had a 5-year survival ~10-fold higher than patients with low-SMS1 plus high-SMS2 expression. SMS1 and SMS2 also had opposing effect on GBM cell survival and 2OHOA’s IC50 correlated with basal SMS1 levels and treatment induced changes in SMS1/SMS2 ratio. SMSs expression disparately affected 2OHOA’s cancer cell proliferation, differentiation, ER-stress and autophagy. Conclusions: SMS1 and SMS2 showed opposite associations with glioma patient survival, glioma cell growth and response to 2OHOA treatment. SMSs signature could constitute a valuable prognostic biomarker, with high SMS1 and low SMS2 being a better disease prognosis. Additionally, low basal SMS1 mRNA levels predict positive response to 2OHOA.

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Section: Discussionmentioning

confidence: 99%

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Fernández‐García

Rosselló

Rodríguez-Lorca

et al. 2019

Cancers

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“…Exon 7b was previously identified in an alternative transcript of the SGMS1 gene. 6 According to the data of the Human Splicing Finder Program, exons 1c, 2c, 3c and 7b contain canonic splicing sites at their ends. Table 1 shows the characterization of the new exons 1c, 2c, 3c and 7b.…”

Section: Detection Of Circrnas Among the Transcripts Of The Human Sgmmentioning

confidence: 99%

“…We established that the transcriptional diversity of the SGMS1 gene is provided by the presence of alternative promoters, alternative polyadenylation and exon splicing. [5][6][7][8][9] In human tissues, transcripts with a 5 0 untranslated region (5 0 UTR) that includes exons 1-6 and exon 7, with a coding region that is localized in exons 7-10 and in a portion of exon 11, and with a 3 0 UTR that stems entirely to the remaining portion of exon 11 are mostly abundant. 8 The multiplicity and complexity of the biological processes that involve the sphingomyelin synthase 1 (SMS1) protein suggest the high specificity of the control of the function of its encoding gene in the individual cells and tissues of organisms.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

et al. 2015

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The human sphingomyelin synthase 1 gene (SGMS1) encodes an essential enzyme that is involved in the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. Among the products of SGMS1, we found new transcripts, circular RNAs (circRNAs), that contain sequences of the gene's 5 0 untranslated region (5 0 UTR). Some of them include the gene's coding region and fragments of introns. An analysis of the abundance of circRNAs in human tissues showed that the largest transcripts were predominantly found in different parts of the brain. circRNAs of rat and mouse sphingomyelin synthase 1 orthologous genes were detected and are highly similar to the human SGMS1 gene transcripts. A quantitative analysis of the abundance of such transcripts also revealed their elevated amount in the brain. A computational analysis of sequences of human circRNAs showed their high potential of binding microRNAs (miRNAs), including the miRNAs that form complexes with Ago proteins and the mRNA of SGMS1. We assume that the circRNAs identified here participate in the regulation of the function of the SGMS1 gene in the brain.

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“…Sphingomyelin synthase 1 (SMS1/SGMS1) and the isoenzyme SMS2 both catalyze the de novo synthesis of sphingomyelin (SM) and diacylglycerol (DAG) from ceramide (Cer) and phosphatidylcholine (PC), while the paralog sphingomyelin synthase-related (SMSr) has no SM synthase activity [2–4]. Several tissue-specific isoforms of SMS1, produced from different promoters as well as through alternative splicing, give rise to two different proteins, of which only one has enzymatic function [5,6]. SMS1 is located in the cis-Golgi apparatus and responsible for the bulk production of SM [2,3,7,8].…”

Section: Introductionmentioning

confidence: 99%

Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice

et al. 2016

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Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.

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Human sphingomyelin synthase 1 gene (SMS1): Organization, multiple mRNA splice variants and expression in adult tissues

Cited by 19 publications

References 56 publications

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice

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