Skip to main content
Log in

The use of alternative polyadenylation in the tissue-specific regulation of human SMS1 gene expression

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Sphingomyelin synthase 1 (SMS1) is an essential enzyme that catalyses the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide in eukaryotic cells. We previously studied the structure of the human SMS1 gene in detail, and identified its numerous transcripts. We revealed mRNA isoforms that varied in the 5′-untranslated region (UTR) and encoded the full-length protein as well as transcripts resulting from alternative combinations of the exons in the gene’s coding region and the 3′-UTR. In the present work, we used real-time PCR data to determine the expression patterns of SMS1 transcripts encoding the full-length protein and the alternative transcripts whose coding region had been interrupted by their alternative exons, which are the conserved portions of intron VII. Our results indicate that the amount of SMS1 transcripts varies considerably between different human tissues. The mechanisms controlling the level of SMS1 transcripts might include tissue-specific intron polyadenylation causing the appearance of truncated transcripts not involved in the synthesis of the full-length protein SMS1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Subathra M, Qureshi A, Luberto C (2011) Sphingomyelin synthases regulate protein trafficking and secretion. PLoS ONE 6(9):e23644. doi:10.1371/journal.pone.0023644

    Article  PubMed  CAS  Google Scholar 

  2. Barceló-Coblijn G, Martin ML, de Almeida RF, Noguera-Salvà MA, Marcilla-Etxenike A, Guardiola-Serrano F, Lüth A, Kleuser B, Halver JE, Escribá PV (2011) Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy. Proc Natl Acad Sci U.S.A. 108:19569–19574

    Article  PubMed  Google Scholar 

  3. Yan N, Ding T, Dong J, Li Y, Wu M (2011) Sphingomyelin synthase overexpression increases cholesterol accumulation and decreases cholesterol secretion in liver cells. Lipids Health Dis 10:46. doi:10.1186/1476-511X-10-46

    Article  PubMed  CAS  Google Scholar 

  4. Shakor AB, Taniguchi M, Kitatani K et al (2011) Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation. J Biol Chem 286:36053–36062

    Article  PubMed  CAS  Google Scholar 

  5. Dergunova LV, Raevskaia NM, Vladychenskaia IP, Limborskaia SA (2003) Structural and functional analyses of the Hfb1, Hmob3 and Hmob33 cDNAs as an example of human brain-specific gene studies. Mol Biol (Mosk) 37:315–324

    Article  CAS  Google Scholar 

  6. Dergunova LV, Vladychenskaia IP, Polukarova LG, Raevskaia NM, Lelikova GP, Limborskaia SA (1998) Features of the structure, expression and chromosomal mapping of the nucleotide sequences of Hmob3 and Hmob33, obtained from a human medulla oblongata cDNA library. Mol Biol (Mosk) 32:249–254

    CAS  Google Scholar 

  7. Vladychenskaya IP, Dergunova LV, Dmitrieva VG, Limborska SA (2004) Human gene MOB:structure specification and aspects of transcriptional activity. Gene 338:257–265

    Article  PubMed  CAS  Google Scholar 

  8. Vladychenskaya IP, Dergunova LV, Limborska SA (2002) In vitro and in silico analysis of the predicted human MOB gene encoding a phylogenetically conserved transmembrane protein. Biomol Eng 18:263–268

    Article  PubMed  CAS  Google Scholar 

  9. Huitema K, van den Dikkenberg J, Brouwers JF, Holthuis JC (2004) Identification of a family of animal sphingomyelin synthases. EMBO J 23:33–44

    Article  PubMed  CAS  Google Scholar 

  10. 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 279:18688–18693

    Article  PubMed  CAS  Google Scholar 

  11. 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 481:65–75

    Article  PubMed  CAS  Google Scholar 

  12. 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:e36

    Article  PubMed  Google Scholar 

  13. Cuccurese M, RussoG Russo A, Pietropaolo C (2005) Alternative splicing and nonsense- mediated mRNA decay regulate mammalian ribosomal gene expression. Nucleic Acids Res 33:5965–5977

    Article  PubMed  CAS  Google Scholar 

  14. Sureau A, Gattoni R, Dooghe Y, Stévenin J, Soret J (2001) SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. EMBO J 20:1785–1796

    Article  PubMed  CAS  Google Scholar 

  15. Holbrook JA, Neu-Yilik G, Hentze MW, Kulozik AE (2004) Nonsense-mediated decayapproaches the clinic. Nat Genet 36:801–808

    Article  PubMed  CAS  Google Scholar 

  16. Lewis BP, Green RE, Brenner SE (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci USA 100:189–192

    Article  PubMed  CAS  Google Scholar 

  17. Weischenfeldt J, Waage J, Tian G, Zhao J, Damgaard I, Jakobsen JS, Kristiansen K, Krogh A, Wang J, Porse BT (2012) Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns. Genome Biol 13:R35. doi:10.1186/gb-2012-13-5-r35

    Article  PubMed  CAS  Google Scholar 

  18. Lareau LF, Brooks AN, Soergel DA, Meng Q, Brenner SE (2007) The coupling of alternative splicing and nonsense-mediated mRNA decay. Adv Exp Med Biol 623:190–211

    Article  PubMed  Google Scholar 

  19. Shi Y (2012) Alternative polyadenylation: new insights from global analyses. RNA 18:2105–2117

    Article  PubMed  CAS  Google Scholar 

  20. Proudfoot NJ (2011) Ending the message: poly(A) signals then and now. Genes Dev 25:1770–1782

    Article  PubMed  CAS  Google Scholar 

  21. Di Giammartino DC, Nishida K, Manley JL (2011) Mechanisms and consequences of alternative polyadenylation. Mol Cell 43:853–866

    Article  PubMed  Google Scholar 

  22. Thomas CP, Andrews JI, Liu KZ (2007) Intronic polyadenylation signal sequences and alternate splicing generate human soluble Flt1 variants and regulate the abundance of soluble Flt1 in the placenta. FASEB J 21:3885–3895

    Article  PubMed  CAS  Google Scholar 

  23. Wang H, Wang P, Sun X, Luo Y, Wang X, Ma D, Wu J (2007) Cloning and characterization of a novel caspase-10 isoform that activates NF-κB activity. Biochim. Biophys Acta (BBA)–General Subjects 1770:1528–1537

    Article  CAS  Google Scholar 

  24. Pan Z, Zhang H, Hague LK, Lee JY, Lutz CS, Tian B (2006) An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism. Gene 366:325–334

    Article  PubMed  CAS  Google Scholar 

  25. Juge F, Audibert A, Benoit B, Simonelig M (2000) Tissue-specific autoregulation of Drosophila suppressor of forked by alternative poly(A) site utilization leads to accumulation of the suppressor of forked protein in mitotically active cells. RNA 6:1529–1538

    Article  PubMed  CAS  Google Scholar 

  26. Dai W, Zhang G, Makeyev EV (2012) RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage. Nucleic Acids Res 40:787–800

    Article  PubMed  CAS  Google Scholar 

  27. Mansfield KD, Keene JD (2012) Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation. Nucleic Acids Res 40:2734–2746

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was partially supported by grants of the Russian Foundation for Basic Research (11-04-00843), and the “Molecular and Cell Biology” Program of the Russian Academy of Sciences, and the Federal Program for Support of Scientific Schools of the Russian Ministry of Science and Education.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lyudmila V. Dergunova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dergunova, L.V., Rozhkova, A.V., Sudarkina, O.Y. et al. The use of alternative polyadenylation in the tissue-specific regulation of human SMS1 gene expression. Mol Biol Rep 40, 6685–6690 (2013). https://doi.org/10.1007/s11033-013-2783-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2783-0

Keywords

Navigation