Alu- and 7SL RNA Analogues Suppress MCF-7 Cell Viability through Modulating the Transcription of Endoplasmic Reticulum Stress Response Genes

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Abstract

11% of the human genome is composed of Alu-retrotransposons, whose transcription by RNA polymerase III (Pol III) leads to the accumulation of several hundreds to thousands of Alu-RNA copies in the cytoplasm. Expression of Alu-RNA Pol III is significantly increased at various levels of stress, and the increase in the Alu-RNA level is accompanied by a suppression of proliferation, a decrease in viability, and induction of apoptotic processes in human cells. However, the question about the biological functions of Pol III Alu-transcripts, as well as their mechanism of action, remains open. In this work, analogues of Alu-RNA and its evolutionary ancestor, 7SL RNA, were synthesized. Transfection of human breast adenocarcinoma MCF-7 cells with the Alu-RNA and 7SL RNA analogues is accompanied by a decrease in viability and by induction of proapoptotic changes in these cells. The analysis of the combined action of these analogues and actinomycin D or tamoxifen revealed that the decreased viability of MCF-7 cells transfected with Alu-RNA and 7SL RNA was due to the modulation of transcription. A whole transcriptome analysis of gene expression revealed that increased gene expression of the transcription regulator NUPR1 (p8), as well as the transcription factor DDIT3 (CHOP), occurs under the action of both the Alu- and 7SL RNA analogues on MCF-7 cells. It has been concluded that induction of proapoptotic changes in human cells under the influence of the Alu-RNA and 7SL RNA analogues is related to the transcriptional activation of the genes of cellular stress factors, including the endoplasmic reticulum stress response factors.

About the authors

D. N. Baryakin

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: baryakindn@niboch.nsc.ru
Россия

D. V. Semenov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: baryakindn@niboch.nsc.ru
Россия

A. V. Savelуeva

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: baryakindn@niboch.nsc.ru
Россия

O. A. Koval

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: baryakindn@niboch.nsc.ru
Россия

I. V. Rabinov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: baryakindn@niboch.nsc.ru
Россия

E. V. Kuligina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: baryakindn@niboch.nsc.ru
Россия

V. A. Riсhter

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: baryakindn@niboch.nsc.ru
Россия

References

  1. International Human Genome Sequencing Consortium // Nature 2001, V.409, №6822, P.860-921
  2. Deininger P.L., Batzer M.A. // Genome Res. 2002, V.12, №10, P.1455-1465
  3. Batzer M.A., Deininger P.L., Hellmann-Blumberg U., Jurka J., Labuda D., Rubin C.M., Schmid C.W., Zietkiewicz E., Zuckerkandl E. // J. Mol. Evol. 1996, V.42, №1, P.3-6
  4. Jurka J., Krnjajic M., Kapitonov V.V., Stenger J.E., Kokhanyy O. // Theor. Popul. Biol. 2002, V.61, №4, P.519-530
  5. Dewannieux M., Esnault C., Heidmann T. // Nat. Genet. 2003, V.35, №1, P.41-48
  6. Batzer M.A., Deininger P.L. // Nat. Rev. Genet. 2002, V.3, №5, P.370-379
  7. Liu W.M., Maraia R.J., Rubin C.M., Schmid C.W. // Nucleic Acids Res. 1994, V.22, №6, P.1087-1095
  8. Liu W.M., Chu W.M., Choudary P.V., Schmid C.W. // Nucleic Acids Res. 1995, V.23, №10, P.1758-1765
  9. Shaikh T.H., Roy A.M., Kim J., Batzer M.A., Deininger P.L. // J. Mol. Biol. 1997, V.271, №2, P.222-234
  10. Maraia R.J., Driscoll C.T., Bilyeu T., Hsu K., Darlington G.J. // Mol. Cell Biol. 1993, V.13, №7, P.4233-4241
  11. Sarrowa J., Chang D.Y., Maraia R.J. // Mol. Cell Biol. 1997, V.17, №3, P.1144-1151
  12. Häsler J., Strub K. // Nucleic Acids Res. 2006, V.34, №19, P.5491-5497
  13. Sakamoto K., Fordis C.M., Corsico C.D., Howard T.H., Howard B.H. // J. Biol. Chem. 1991, V.266, №5, P.3031-3038
  14. Chu W.M., Ballard R., Carpick B.W., Williams B.R., Schmid C.W. // Mol. Cell Biol. 1998, V.18, №1, P.58-68
  15. Rubin C.M., Kimura R.H., Schmid C.W. // Nucleic Acids Res. 2002, V.30, №14, P.3253-3261
  16. Hasler J., Strub K. // Nucleic Acids Res. 2006, V.34, №8, P.2374-2385
  17. Bovia F., Wolff N., Ryser S., Strub K. // Nucleic Acids Res. 1997, V.25, №2, P.318-326
  18. Chang D.Y., Hsu K., Maraia R.J. // Nucleic Acids Res. 1996, V.24, №21, P.4165-4170
  19. Mariner P.D., Walters R.D., Espinoza C.A., Drullinger L.F., Wagner S.D., Kugel J.F., Goodrich J.A. // Molecular Cell 2008, V.29, №4, P.499-509
  20. Yakovchuk P., Goodrich J.A., Kugel J.F. // Proc. Natl. Acad. Sci. USA. 2009, V.106, №14, P.5569-5574
  21. Kaneko H., Dridi S., Tarallo V., Gelfand B.D., Fowler B.J., Cho W.G., Kleinman M.E., Ponicsan S.L., Hauswirth W.W., Chiodo V.A. // Nature 2011, V.471, №7338, P.325-330
  22. Tarallo V., Hirano Y., Gelfand B.D., Dridi S., Kerur N., Kim Y., Cho W.G., Kaneko H., Fowler B.J., Bogdanovich S. // Cell. 2012, V.149, №4, P.847-859
  23. Galluzzi L., Vitale I., Kepp O., Seror C., Hangen E., Perfettini J.L., Modjtahedi N., Kroemer G. // Methods Enzymol. 2008, V.442, P.355-374
  24. Stepanov G.A., Semenov D.V., Savelyeva A.V., Kuligina E.V., Koval O.A., Rabinov I.V., Richter V.A. // Biomed. Res. 2013, P.e.656158
  25. Kroemer G., Galluzzi L., Brenner C. // Physiol. Rev. 2007, V.87, №1, P.99-163
  26. Demchenko A.P. // Exp. Oncol. 2012, V.34, №3, P.263-268
  27. Berridge M.V., Herst P.M., Tan A.S. // Biotechnol. Annu. Rev. 2005, V.11, P.127-152
  28. Siddik Z.H. // Oncogene. 2003, V.22, №47, P.7265-7279
  29. Balachandran S., Barber G.N. // Meth. Mol. Biol. 2007, V.383, P.277-301
  30. Lindner D.J., Kolla V., Kalvakolanu D.V., Borden E.C. // Mol. Cell Biochem. 1997, V.167, №1-2, P.169-177
  31. Iacopino F., Robustelli della Cuna G., Sica G. // Int. J. Cancer. 1997, V.71, №6, P.1103-1108
  32. Der S.D., Zhou A., Williams B.R., Silverman R.H. // Proc. Natl. Acad. Sci. USA. 1998, V.95, №26, P.15623-15628
  33. Goruppi S., Iovanna J.L. // J. Biol. Chem. 2010, V.285, №3, P.1577-1581
  34. Guo X., Wang W., Hu J., Feng K., Pan Y., Zhang L., Feng Y. // Anat. Rec. (Hoboken). 2012, V.295, №12, P.2114-2121
  35. Carracedo A., Lorente M., Egia A., Blázquez C., García S., Giroux V., Malicet C., Villuendas R., Gironella M., González-Feria L. // Cancer Cell. 2006, V.9, №4, P.301-312
  36. Tabas I., Ron D. // Nat. Cell Biol. 2011, V.13, №3, P.184-190
  37. Riemer J., Appenzeller-Herzog C., Johansson L., Bodenmiller B., Hartmann-Petersen R., Ellgaard L. // Proc. Natl. Acad. Sci. USA. 2009, V.106, №35, P.14831-14836
  38. Siu F., Chen C., Zhong C., Kilberg M.S. // J. Biol. Chem. 2001, V.276, №51, P.48100-48107

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Copyright (c) 2013 Baryakin D.N., Semenov D.V., Savelуeva A.V., Koval O.A., Rabinov I.V., Kuligina E.V., Riсhter V.A.

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