Russian Journal of Bioorganic Chemistry

, Volume 44, Issue 1, pp 90–103 | Cite as

Apoptotic Endonuclease EndoG Induces Alternative Splicing of Telomerase TERT Catalytic Subunit, Caspase-2, DNase I, and BCL-x in Human, Murine, and Rat CD4+ T Lymphocytes

  • D. D. Zhdanov
  • Y. A. Gladilina
  • D. V. Grishin
  • V. S. Pokrovsky
  • M. V. Pokrovskaya
  • S. S. Aleksandrova
  • N. N. Sokolov


Apoptotic endonuclease EndoG plays a key role in the alternative splicing of mRNA of human TERT telomerase catalytic subunit. The aim of this work was to test the ability of EndoG to induce alternative splicing of mRNA of other genes and in other organisms. To determine new mRNA splice-variants, EndoG overexpression was induced in human, mouse and rat CD4+-T-lymphocytes followed by sequencing of total RNA of these cells. Sequencing results showed that besides TERT, EndoG induced alternative splicing of deoxyribonuclease I (DNase I), caspase-2 (Casp-2) and BCL-x. The expression level of EndoG strongly correlated with mRNA splicing-variants of TERT, DNase I, Casp-2, and BCL-x in intact CD4+-T cells of healthy donors as well as different lines of mice and rats. EndoG overexpression induced down-regulation of fulllength mRNAs of TERT, DNase I, Casp-2, and BCL-x and up-regulation of their short-length mRNAs. Alternative splicing of studied mRNAs resulted in down-regulation of enzymatic activity of proteins in vitro and in vivo. The results of this work confirm the ability of endonuclease EndoG to induce alternative splicing of several mRNAs in human, mice and rats.


alternative splicing EndoG TERT Casp-2 DNase I BCL-x 



alternative splicing


telomerase reverse transcriptase


endonuclease G


EndoG-produced oligonucleotide




green fluorescent protein


telomeric repeats amplification protocol


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  1. 1.
    Kim, E., Magen, A., and Ast, G., Nucleic Acids Res., 2007, vol. 35, p. 125.CrossRefPubMedGoogle Scholar
  2. 2.
    Makeyev, E.V., Zhang, J., Carrasco, M.A., and Maniatis, T., Mol. Cell, 2007, vol. 27, pp. 435–448.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jin, Y., Yang, Y., and Zhang, P., RNA Biol., vol. 8, pp. 450–457.Google Scholar
  4. 4.
    Chen, M. and Manley, J.L., Nat. Rev. Mol. Cell Biol., 2009, vol. 10, p. 741.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhdanov, D.D., Vasina, D.A., Orlova, E.V., Orlova, V.S., Pokrovskaya, M.V., Aleksandrova, S.S., and Sokolov, N.N., Biomed. Khim., 2016, vol. 62, pp. 544–554.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhdanov, D.D., Vasina, D.A., Orlova, V.S., Gotovtseva, V.Y., Bibikova, M.V., Pokrovsky, V.S., Pokrovskaya, M.V., Aleksandrova, S.S., and Sokolov, N.N., Biomed. Khim., 2016, vol. 62, pp. 239–250.CrossRefPubMedGoogle Scholar
  7. 7.
    Khanna, A. and Stamm, S., RNA Biol., 2016, vol. 7, pp. 480–485.CrossRefGoogle Scholar
  8. 8.
    Bauman, J., Jearawiriyapaisarn, N., and Kole, R., Oligonucleotides, 2009, vol. 19, pp. 1–13.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ulaner, G.A., Hu, J.F., Vu, T.H., Oruganti, H., Giudice, L.C., and Hoffman, A.R., Int. J. Cancer, 2000, vol. 85, pp. 330–335.CrossRefPubMedGoogle Scholar
  10. 10.
    Aravind, L., Dixit, V.M., and Koonin, E.V., Trends Biochem. Sci., 1999, vol. 24, pp. 47–53.CrossRefPubMedGoogle Scholar
  11. 11.
    Yin, X., Apostolov, E.O., Hahs, V.S., Wang, X., Bogdanov, K.V, Buzder, T., Stewart, A.G., and Basnakian, A.G., J. Am. Soc. Nephrol., 2007, vol. 18, pp. 2544–2553.CrossRefPubMedGoogle Scholar
  12. 12.
    Vasina, D.A., Zhdanov, D.D., Orlova, E.V., Orlova, V.S., Pokrovskaya, M.V., Aleksandrova, S.S., and Sokolov, N.N., Biochemistry (Moscow), 2017, vol. 82, pp. 24–37.CrossRefGoogle Scholar
  13. 13.
    Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., and Hoffman, A.R., Cancer Res., 1998, vol. 58, pp. 4168–4172.PubMedGoogle Scholar
  14. 14.
    Listerman, I., Sun, J., Gazzaniga, F.S., Lukas, J.L., and Blackburn, E.H., Cancer Res., 2013, vol. 73, pp. 2817–2828.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Robertson, J.D., Enoksson, M., Suomela, M., Zhivotovsky, B., and Orrenius, S., J. Biol. Chem., 2002, vol. 277, pp. 29803–29809.CrossRefPubMedGoogle Scholar
  16. 16.
    Vakifahmetoglu, H., Olsson, M., Tamm, C., Heidari, N., Orrenius, S., and Zhivotovsky, B., Cell Death Differ., 2008, vol. 15, pp. 555–566.CrossRefPubMedGoogle Scholar
  17. 17.
    Fushimi, K., Ray, P., Kar, A., Wang, L., Sutherland, L.C., and Wu, J.Y., Proc. Natl. Acad. Sci. U. S. A., 2008, vol. 105, pp. 15708–15713.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tu, S., McStay, G.P., Boucher, L.-M., Mak, T., Beere, H.M., and Green, D.R., Nat. Cell Biol., 2006, vol. 8, pp. 72–77.CrossRefPubMedGoogle Scholar
  19. 19.
    Peart, M.J., Tainton, K.M., Ruefli, A.A., Dear, A.E., Sedelies, K.A., O’Reilly, L.A., Waterhouse, N.J., Trapani, J.A., and Johnstone, R.W., Cancer Res., 2003, vol. 63, pp. 4460–4471.PubMedGoogle Scholar
  20. 20.
    Wotawa, A., Solier, S., Logette, E., Solary, E., and Corcos, L., Cancer Lett., 2002, vol. 185, pp. 181–189.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhivotovsky, B. and Orrenius, S., Biochem. Biophys. Res. Commun., 2005, vol. 331, pp. 859–867.CrossRefPubMedGoogle Scholar
  22. 22.
    Wang, L., Miura, M., Bergeron, L., Zhu, H., and Yuan, J., Cell, 1994, vol. 78, pp. 739–750.CrossRefPubMedGoogle Scholar
  23. 23.
    Apostolov, E.O., Ray, D., Alobuia, W.M., Mikhailova, M.V., Wang, X., Basnakian, A.G., and Shah, S.V., Am. J. Physiol. Heart Circ. Physiol., 2011, vol. 300, pp. 1997–2004.CrossRefGoogle Scholar
  24. 24.
    Lacks, S.A., J. Biol. Chem., 1981, vol. 256, pp. 2644–2648.PubMedGoogle Scholar
  25. 25.
    Basnakian, A.G., Apostolov, E.O., Yin, X., Napirei, M., Mannherz, H.G., and Shah, S.V., J. Am. Soc. Nephrol., 2005, vol. 16, pp. 697–702.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhdanov, D.D., Fahmi, T., Wang, X., Apostolov, E.O., Sokolov, N.N., Javadov, S., and Basnakian, A.G., DNA Cell Biol., 2015, vol. 34, pp. 316–326.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Korsmeyer, S.J., Trends Genet., 1995, vol. 11, pp. 101–105.CrossRefPubMedGoogle Scholar
  28. 28.
    Chao, D.T., Linette, G.P., Boise, L.H., White, L.S., Thompson, C.B., and Korsmeyer, S.J., J. Exp. Med., 1995, vol. 182, pp. 821–828.CrossRefPubMedGoogle Scholar
  29. 29.
    Silva, M., Richard, C., Benito, A., Sanz, C., Olalla, I., and Fernandez-Luna, J.L., N. Engl. J. Med., 1998, vol. 338, pp. 564–571.CrossRefPubMedGoogle Scholar
  30. 30.
    Shkreta, L., Froehlich, U., Paquet, E.R., Toutant, J., Elela, S.A., and Chabot, B., Mol. Cancer Ther., 2008, vol. 7, pp. 1398–1409.CrossRefPubMedGoogle Scholar
  31. 31.
    Shkreta, L., Michelle, L., Toutant, J., Tremblay, M.L., and Chabot, B., J. Biol. Chem., 2011, vol. 286, pp. 331–340.CrossRefPubMedGoogle Scholar
  32. 32.
    Cheranova, D., Gibson, M., Chaudhary, S., Zhang, L.Q., Heruth, D.P., Grigoryev, D.N., and Qing, Ye.S., J. Vis. Exp., 2013.Google Scholar
  33. 33.
    Zhang, L.Q., Cheranova, D., Gibson, M., Ding, S., Heruth, D.P., Fang, D., and Ye, S.Q., PLoS One, 2012, vol. 7, p. e31229.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Heruth, D.P., Gibson, M., Grigoryev, D.N., Zhang, L.Q., and Ye, S.Q., Cell Biosci., 2012, vol. 2, p. 43.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D.R., Pimentel, H., Salzberg, S.L., Rinn, J.L., and Pachter, L., Nat. Protoc., 2012, vol. 7, pp. 562–578.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Laemmli, U.K., Nature, 1970, vol. 227, pp. 680–685.CrossRefPubMedGoogle Scholar
  37. 37.
    Hofnagel, O., Luechtenborg, B., Stolle, K., Lorkowski, S., Eschert, H., Plenz, G., and Robenek, H., Arterioscler. Thromb. Vasc. Biol., 2004, vol. 24, pp. 1789–1795.CrossRefPubMedGoogle Scholar
  38. 38.
    Basnakian, A.G., Singh, A.B., and Shah, S.V., Gene, 2002, vol. 289, pp. 87–96.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • D. D. Zhdanov
    • 1
  • Y. A. Gladilina
    • 1
  • D. V. Grishin
    • 1
  • V. S. Pokrovsky
    • 1
    • 2
  • M. V. Pokrovskaya
    • 1
  • S. S. Aleksandrova
    • 1
  • N. N. Sokolov
    • 1
  1. 1.Orekhovich Institute of Biomedical ChemistryMoscowRussia
  2. 2.Blokhin Cancer Research CenterMoscowRussia

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