Biochemistry (Moscow)

, Volume 78, Issue 2, pp 157–165 | Cite as

Cap-independent translation initiation of Apaf-1 mRNA based on a scanning mechanism is determined by some features of the secondary structure of its 5′ untranslated region

  • D. E. Andreev
  • S. E. Dmitriev
  • I. M. Terenin
  • I. N. ShatskyEmail author
Accelerated Publication


We have earlier shown that the 5′-untranslated region (5′ UTR) of the mRNA coding for activation factor of apoptotic peptidase 1 (Apaf-1) can direct translation in vivo by strictly 5′ end-dependent way even in the absence of m7G-cap. Dependence of translational efficiency on the cap availability for this mRNA turned out to be relatively low. In this study we demonstrate that this surprising phenomenon is determined the 5′-proximal part (domains I and II) of highly structured Apaf-1 5′ UTR. Remarkably, domain II by itself was able to reduce dependence of the mRNA on the cap on its transferring to a short 5′ UTR derived from a standard vector. We suggest that the low cap-dependence inherent to some cellular mRNAs may have an important physiological significance under those stress conditions when the function of cap-binding factor eIF4E is impaired.

Key words

protein biosynthesis translational control cellular IRES-elements cap-independent translation Apaf-1 mRNA 



apoptotic peptidase activating factor 1


cap-independent translational enhancers


eukaryotic initiation factor


internal ribosome entry site

5′ UTR

5′-untranslated region


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cully, M., and Downward, J. (2009) Biochem. Soc. Trans., 37, 284–288.PubMedCrossRefGoogle Scholar
  2. 2.
    Polunovsky, V. A., and Bitterman, P. B. (2006) RNA Biol., 3, 10–17.PubMedCrossRefGoogle Scholar
  3. 3.
    Averous, J., and Proud, C. G. (2006) Oncogene, 25, 6423–6435.PubMedCrossRefGoogle Scholar
  4. 4.
    Robert, F., and Pelletier, J. (2009) Expert Opin. Ther. Targets, 13, 1279–1293.PubMedCrossRefGoogle Scholar
  5. 5.
    Silvera, D., Formenti, S. C., and Schneider, R. J. (2010) Nat. Rev. Cancer, 10, 254–266.PubMedCrossRefGoogle Scholar
  6. 6.
    Proud, C. G. (2009) Biochem. Soc. Trans., 37, 227–231.PubMedCrossRefGoogle Scholar
  7. 7.
    Lin, T. A., Kong, X., Haystead, T. A., Pause, A., Belsham, G., Sonenberg, N., and Lawrence, J. C., Jr. (1994) Science, 266, 653–656.PubMedCrossRefGoogle Scholar
  8. 8.
    Pause, A., Belsham, G. J., Gingras, A. C., Donze, O., Lin, T. A., Lawrence, J. C., Jr., and Sonenberg, N. (1994) Nature, 371, 762–767.PubMedCrossRefGoogle Scholar
  9. 9.
    Poulin, F., Gingras, A. C., Olsen, H., Chevalier, S., and Sonenberg, N. (1998) J. Biol. Chem., 273, 14002–14007.PubMedCrossRefGoogle Scholar
  10. 10.
    Reiling, J. H., and Sabatini, D. M. (2006) Oncogene, 25, 6373–6383.PubMedCrossRefGoogle Scholar
  11. 11.
    Morley, S. J., Coldwell, M. J., and Clemens, M. J. (2005) Cell. Death Differ., 12, 571–584.PubMedCrossRefGoogle Scholar
  12. 12.
    Schafer, Z. T., and Kornbluth, S. (2006) Dev. Cell., 10, 549–561.PubMedCrossRefGoogle Scholar
  13. 13.
    Coldwell, M. J., Mitchell, S. A., Stoneley, M., MacFarlane, M., and Willis, A. E. (2000) Oncogene, 19, 899–905.PubMedCrossRefGoogle Scholar
  14. 14.
    Mitchell, S. A., Spriggs, K. A., Coldwell, M. J., Jackson, R. J., and Willis, A. E. (2003) Mol. Cell., 11, 757–771.PubMedCrossRefGoogle Scholar
  15. 15.
    Ungureanu, N. H., Cloutier, M., Lewis, S. M., de Silva, N., Blais, J. D., Bell, J. C., and Holcik, M. (2006) J. Biol. Chem., 281, 15155–15163.PubMedCrossRefGoogle Scholar
  16. 16.
    Macejak, D. G., and Sarnow, P. (1991) Nature, 353, 90–94.PubMedCrossRefGoogle Scholar
  17. 17.
    Holcik, M., and Sonenberg, N. (2005) Nat. Rev. Mol. Cell. Biol., 6, 318–327.PubMedCrossRefGoogle Scholar
  18. 18.
    Komar, A. A., and Hatzoglou, M. (2005) J. Biol. Chem., 280, 23425–23428.PubMedCrossRefGoogle Scholar
  19. 19.
    Graber, T. E., and Holcik, M. (2007) Mol. Biosyst., 3, 825–834.PubMedCrossRefGoogle Scholar
  20. 20.
    Spriggs, K. A., Stoneley, M., Bushell, M., and Willis, A. E. (2008) Biol. Cell, 100, 27–38.PubMedCrossRefGoogle Scholar
  21. 21.
    Komar, A. A., and Hatzoglou, M. (2011) Cell. Cycle, 10, 229–240.PubMedCrossRefGoogle Scholar
  22. 22.
    Andreev, D. E., Dmitriev, S. E., Terenin, I. M., Prassolov, V. S., Merrick, W. C., and Shatsky, I. N. (2009) Nucleic Acids Res., 37, 6135–6147.PubMedCrossRefGoogle Scholar
  23. 23.
    Stoneley, M., Paulin, F. E., Le Quesne, J. P., Chappell, S. A., and Willis, A. E. (1998) Oncogene, 16, 423–428.PubMedCrossRefGoogle Scholar
  24. 24.
    Dmitriev, S. E., Andreev, D. E., Ad’yanova, Z. V., Terenin, I. M., and Shatsky, I. N. (2009) Mol. Biol. (Moscow), 43, 108–113.Google Scholar
  25. 25.
    Barreau, C., Dutertre, S., Paillard, L., and Osborne, H. B. (2006) RNA, 12, 1790–1793.PubMedCrossRefGoogle Scholar
  26. 26.
    Dmitriev, S. E., Andreev, D. E., Terenin, I. M., Olovnikov, I. A., Prassolov, V. S., Merrick, W. C., and Shatsky, I. N. (2007) Mol. Cell. Biol., 27, 4685–4697.PubMedCrossRefGoogle Scholar
  27. 27.
    Vassilenko, K. S., Alekhina, O. M., Dmitriev, S. E., Shatsky, I. N., and Spirin, A. S. (2011) Nucleic Acids Res., 39, 5555–5567.PubMedCrossRefGoogle Scholar
  28. 28.
    De Gregorio, E., Preiss, T., and Hentze, M. W. (1998) RNA, 4, 828–836.PubMedCrossRefGoogle Scholar
  29. 29.
    Ali, I. K., McKendrick, L., Morley, S. J., and Jackson, R. J. (2001) EMBO J., 20, 4233–4242.PubMedCrossRefGoogle Scholar
  30. 30.
    Gunnery, S., Maivali, U., and Mathews, M. B. (1997) J. Biol. Chem., 272, 21642–21646.PubMedCrossRefGoogle Scholar
  31. 31.
    Shatsky, I. N., Dmitriev, S. E., Terenin, I. M., and Andreev, D. E. (2010) Mol. Cells, 30, 285–293.PubMedCrossRefGoogle Scholar
  32. 32.
    Terenin, I. M., Andreev, D. E., Dmitriev, S. E., and Shatsky, I. N. (2012) Nucleic Acids Res., doi: 10.1093/nar/gks 1282.Google Scholar
  33. 33.
    Lerner, R. S., and Nicchitta, C. V. (2006) RNA, 12, 775–789.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  • D. E. Andreev
    • 1
  • S. E. Dmitriev
    • 1
  • I. M. Terenin
    • 1
  • I. N. Shatsky
    • 1
    Email author
  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations