Cell and Tissue Research

, Volume 372, Issue 1, pp 33–40 | Cite as

Developmental stage-specific expression of genes for sphingomyelin synthase in rat brain

  • Ivan B. Filippenkov
  • Timur A. Kolomin
  • Svetlana A. Limborska
  • Lyudmila V. Dergunova
Regular Article
  • 185 Downloads

Abstract

Sphingomyelin synthase genes (Sgms1 and Sgms2) encode the vital enzymes that participate in the processes of membrane transport, cell proliferation and apoptosis. We previously determined the exon–intron structure of Sgms1 and some features of its expression in human and rodent tissues. The circular RNAs (circRNAs) emerging from exons of the 5′-untranslated region (5′-UTR) of Sgms1 were determined. These circRNAs are represented at a high level in the adult brain. Here, we demonstrate that, in contrast to Sgms1, Sgms2 does not contain the multi-exon 5′-UTR but encodes circRNAs, which are composed of the coding region of the gene and are expressed at a low level. We present a study of the expression of sphingomyelin synthase genes in rat brain at embryonic days 7, 9, 13, 17 and 21 and in adult rat brain. In contrast to Sgms1, Sgms2 is expressed at a significantly low level in adult brain. In embryonic rat brain, the mRNA expression of sphingomyelin synthase genes is varied in a developmental stage-specific manner. The level of Sgms1 mRNAs, differing by 5′-UTR—in the formation of which alternative promoters can participate—changes significantly during the process of embryonic development. The expression of circRNAs of Sgms1 was significantly raised during rat embryonic brain development. We assume that the circRNAs are involved in the regulation of sphingomyelin synthase activity in rat brain in different developmental stages.

Keywords

Sphingomyelin synthase genes Developmental stage-specific expression Alternative promoters mRNA Circular RNA 

Notes

Acknowledgments

We thank the Russian Foundation for Basic Research for support.

Compliance with ethical standards

Ethical approval

All applicable international guidelines for the care and use of animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

441_2017_2762_MOESM1_ESM.xlsx (11 kb)
Tab. S1 (XLSX 11 kb)
441_2017_2762_MOESM2_ESM.xlsx (15 kb)
Tab. S2 (XLSX 14 kb)
441_2017_2762_MOESM3_ESM.xlsx (9 kb)
Tab. S3 (XLSX 8 kb)
441_2017_2762_MOESM4_ESM.xlsx (27 kb)
Tab. S4 (XLSX 27 kb)
441_2017_2762_MOESM5_ESM.xlsx (38 kb)
Tab. S5 (XLSX 38 kb)
441_2017_2762_MOESM6_ESM.xlsx (11 kb)
Tab. S6 (XLSX 11 kb)
441_2017_2762_MOESM7_ESM.xlsx (10 kb)
Tab. S7 (XLSX 10 kb)
441_2017_2762_MOESM8_ESM.xlsx (9 kb)
Tab. S8 (XLSX 9 kb)
441_2017_2762_MOESM9_ESM.xlsx (9 kb)
Tab. S9 (XLSX 9 kb)
441_2017_2762_MOESM10_ESM.xlsx (10 kb)
Tab. S10 (XLSX 10 kb)

References

  1. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55(4):611–622.  https://doi.org/10.1373/clinchem.2008.112797 CrossRefPubMedGoogle Scholar
  2. Chen W, Schuman E (2016) Circular RNAs in brain and other tissues: a functional enigma. Trends Neurosci 39(9):597–604.  https://doi.org/10.1016/j.tins.2016.06.006 CrossRefPubMedGoogle Scholar
  3. Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53(6):359–365.  https://doi.org/10.1136/jmedgenet-2016-103758 CrossRefPubMedGoogle Scholar
  4. Cheng EC, Lin H (2013) Repressing the repressor: a lincRNA as a MicroRNA sponge in embryonic stem cell self-renewal. Dev Cell 25(1):1–2.  https://doi.org/10.1016/j.devcel.2013.03.020 CrossRefPubMedGoogle Scholar
  5. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159.  https://doi.org/10.1006/abio.1987.9999 CrossRefPubMedGoogle Scholar
  6. Dang Y, Yan L, Hu B, Fan X, Ren Y, Li R, Lian Y, Yan J, Li Q, Zhang Y, Li M, Ren X, Huang J, Wu Y, Liu P, Wen L, Zhang C, Huang Y, Tang F, Qiao J (2016) Tracing the expression of circular RNAs in human pre-implantation embryos. Genome Biol 17(1):130.  https://doi.org/10.1186/s13059-016-0991-3 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Denzler R, Agarwal V, Stefano J, Bartel DP, Stoffel M (2014) Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell 54(5):766–776.  https://doi.org/10.1016/j.molcel.2014.03.045 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Dergunova LV, Rozhkova AV, Sudarkina OY, Limborska SA (2013) The use of alternative polyadenylation in the tissue-specific regulation of human SMS1 gene expression. Mol Biol Rep 40(12):6685–6690.  https://doi.org/10.1007/s11033-013-2783-0 CrossRefPubMedGoogle Scholar
  9. Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang F, Huang Y (2015) Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol 16:148.  https://doi.org/10.1186/s13059-015-0706-1 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Filippenkov IB, Sudarkina OY, Limborska SA, Dergunova LV (2015) Circular RNA of the human sphingomyelin synthase 1 gene: multiple splice variants, evolutionary conservatism and expression in different tissues. RNA Biol 12(9):1030–1042.  https://doi.org/10.1080/15476286.2015.1076611 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Filippenkov IB, Kalinichenko EO, Limborska SA, Dergunova LV (2017) Circular RNAs-one of the enigmas of the brain. Neurogenetics 18(1):1–6.  https://doi.org/10.1007/s10048-016-0490-4 CrossRefPubMedGoogle Scholar
  12. Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, Kjems J (2011) miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J 30(21):4414–4422.  https://doi.org/10.1038/emboj.2011.359 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388.  https://doi.org/10.1038/nature11993 CrossRefPubMedGoogle Scholar
  14. Huang C, Shan G (2015) What happens at or after transcription: insights into circRNA biogenesis and function. Transcription 6(4):61–64.  https://doi.org/10.1080/21541264.2015.1071301 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP (2011) In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147(2):382–395.  https://doi.org/10.1016/j.cell.2011.09.032 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kartha RV, Subramanian S (2014) Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet 5:8.  https://doi.org/10.3389/fgene.2014.00008 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Li Z, Hailemariam TK, Zhou H, Li Y, Duckworth DC, Peake DA, Zhang Y, Kuo MS, Cao G, Jiang XC (2007) Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization. Biochim Biophys Acta 1771(9):1186–1194.  https://doi.org/10.1016/j.bbalip.2007.05.007 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, et al. (2015)Exon-intron circular RNAs regulate transcription in the nucleus.Nat Struct Mol Biol 22:256–264Google Scholar
  19. Masek T, Vopalensky V, Suchomelova P, Pospisek M (2005) Denaturing RNA electrophoresis in TAE agarose gels. Anal Biochem 336(1):46–50.  https://doi.org/10.1016/j.ab.2004.09.010 CrossRefPubMedGoogle Scholar
  20. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338.  https://doi.org/10.1038/nature11928 CrossRefPubMedGoogle Scholar
  21. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30(9):e36CrossRefPubMedPubMedCentralGoogle Scholar
  22. Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP (2004) Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper--excel-based tool using pair-wise correlations. Biotechnol Lett 26(6):509–515CrossRefPubMedGoogle Scholar
  23. Rozhkova AV, Dmitrieva VG, Zhapparova ON, Sudarkina OY, Nadezhdina ES, Limborska SA, Dergunova LV (2011) Human sphingomyelin synthase 1 gene (SMS1): organization, multiple mRNA splice variants and expression in adult tissues. Gene 481(2):65–75.  https://doi.org/10.1016/j.gene.2011.04.010 CrossRefPubMedGoogle Scholar
  24. Rozhkova AV, Filippenkov IB, Sudarkina OY, Limborska SA, Dergunova LV (2015) Alternative promoters located in SGMS1 gene introns participate in regulation of its expression in human tissues. Mol Biol (Mosk) 49(2):325–333CrossRefGoogle Scholar
  25. Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, Hanan M, Behm M, Bartok O, Ashwal-Fluss R, Herzog M, Schreyer L, Papavasileiou P, Ivanov A, Öhman M, Refojo D, Kadener S, Rajewsky N (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885.  https://doi.org/10.1016/j.molcel.2015.03.027 CrossRefPubMedGoogle Scholar
  26. Salzman J (2016) Circular RNA expression: its potential regulation and function. Trends Genet 32(5):309–316.  https://doi.org/10.1016/j.tig.2016.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Tafesse FG, Huitema K, Hermansson M, van der Poel S, van den Dikkenberg J, Uphoff A, Somerharju P, Holthuis JC (2007) Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. J Biol Chem 282(24):17537–17547.  https://doi.org/10.1074/jbc.M702423200 CrossRefPubMedGoogle Scholar
  28. Veno MT, Hansen TB, Veno ST, Clausen BH, Grebing M, Finsen B, Holm IE, Kjems J (2015) Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol 16:245.  https://doi.org/10.1186/s13059-015-0801-3 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Wittmann A, Grimm MO, Scherthan H, Horsch M, Beckers J, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Ford SJ, Burton NC, Razansky D, Trümbach D, Aichler M, Walch AK, Calzada-Wack J, Neff F, Wurst W, Hartmann T, Floss T (2016) Sphingomyelin synthase 1 is essential for male fertility in mice. PLoS ONE 11(10):e0164298.  https://doi.org/10.1371/journal.pone.0164298 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Yamaoka S, Miyaji M, Kitano T, Umehara H, Okazaki T (2004) Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells. J Biol Chem 279(18):18688–18693.  https://doi.org/10.1074/jbc.M401205200 CrossRefPubMedGoogle Scholar
  31. Yang Z, Jean-Baptiste G, Khoury C, Greenwood MT (2005) The mouse sphingomyelin synthase 1 (SMS1) gene is alternatively spliced to yield multiple transcripts and proteins. Gene 363:123–132.  https://doi.org/10.1016/j.gene.2005.07.036 CrossRefPubMedGoogle Scholar
  32. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, Akbalik G, Wang M, Glock C, Quedenau C, Wang X, Hou J, Liu H, Sun W, Sambandan S, Chen T, Schuman EM, Chen W (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18(4):603–610.  https://doi.org/10.1038/nn.3975 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL (2013) Circular intronic long noncoding RNAs. Mol Cell 51(6):792–806.  https://doi.org/10.1016/j.molcel.2013.08.017 CrossRefPubMedGoogle Scholar
  34. Zhang Y, Xue W, Li X, Zhang J, Chen S, Zhang JL, Yang L, Chen LL (2016) The biogenesis of nascent circular RNAs. Cell Rep 15(3):611–624.  https://doi.org/10.1016/j.celrep.2016.03.058 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Ivan B. Filippenkov
    • 1
  • Timur A. Kolomin
    • 1
  • Svetlana A. Limborska
    • 1
    • 2
  • Lyudmila V. Dergunova
    • 1
    • 2
  1. 1.Institute of Molecular Genetics, Russian Academy of SciencesMoscowRussia
  2. 2.Pirogov Russian National Research Medical UniversityMoscowRussia

Personalised recommendations