Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

The polyadenylation inhibitor cordycepin (3′dA) causes a decline in c-MYC mRNA levels without affecting c-MYC protein levels

Oncogene volume 18, pages 117–125 (1999)Cite this article

Abstract

Study of the distribution of the poly(A) tail length of c-myc mRNA in several cell lines revealed a distinct, prevailing population with short poly(A) tails, derived through sequential deadenylation. To elucidate the possible in vivo function of this distinct short tailed c-myc mRNA population, the polyadenylation inhibitor cordycepin was used. This resulted in a decline in steady state c-myc mRNA levels with the remaining messenger mostly oligoadenylated. However, c-MYC proteins did not follow the reduction of the c-myc mRNA. On the other hand, in cells exposed to physiological agents known to downregulate c-myc expression, the reduction of mRNA steady state levels, was reflected upon c-MYC protein levels. The dissociation between c-myc mRNA and protein levels caused by cordycepin was not due to the stabilization of the c-MYC proteins and was not an indiscriminate effect since in the presence of cordycepin, c-fos mRNA and protein levels concomitantly declined. Our data indicate that under these conditions, a long poly(A) tail is not instrumental for c-myc mRNA translation and furthermore, the discrepancy in the steady state of c-myc mRNA level: c-MYC protein ratio between control cells and cells treated with cordycepin indicates that c-myc mRNA is subjected to translational control.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Bachvarova RF. . 1992 Cell 69: 895–897.

    Article  CAS  PubMed  Google Scholar 

  • Ballantine JEM and Woodland HR. . 1985 FEBS Lett. 180: 224–228.

  • Beach R and Ross J. . 1978 J. Biol. Chem. 253: 2628–2632.

  • Bernstein J, Shefler I and Elroy-Stein O. . 1997 J. Biol. Chem. 270: 10559–10565.

  • Black BL, Lu J and Olson EN. . 1997 Mol. Cell. Biol. 17: 2756–2763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brewer G and Ross J. . 1990 Meth. Enzymol. 181: 202–209.

  • Bravo R, Burckhardt J, Curran T and Muller R. . 1986 EMBO J. 5: 695–700.

  • Chen CY and Shyu AB. . 1994 Mol. Cell. Biol. 14: 8471–8482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CY and Shyu AB. . 1995 TIBS 20: 465–470.

  • Chomczynski P and Sacchi N. . 1987 Analyt. Biochem. 162: 156–159.

  • Christensen AK, Kahn LE and Bourne CM. . 1987 Am. J. Anat. 178: 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Dani Ch, Mechti N, Piechaczyk M, Lebleu B, Jeanteur P and Blanchard JM. . 1985 Proc. Natl. Acad. Sci. USA 82: 4896–4899.

  • Darveau A, Pelletier J and Sonenberg N. . 1985 Proc. Natl. Acad. Sci. USA 82: 2315–2319.

  • Decker CJ and Parker R. . 1994 TIBS 19: 336–340.

  • Dehlin E, von Gabain A, Alm G, Dingelmaier R and Resnekov O. . 1996 Mol. Cell. Biol. 16: 468–474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallie DR. . 1991 Genes Dev. 5: 2108–2116.

  • Grafi G, Sela I and Galili G. . 1993 Mol. Cell. Biol. 13: 3487–3493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greenberg ME and Ziff EB. . 1984 Nature 311: 433–438.

    Article  CAS  PubMed  Google Scholar 

  • Han J, Brown T and Beutler B. . 1990 J. Exp. Med. 171: 465–475.

  • Hann SR, Thompson CB and Eiseman RN. . 1985 Nature 314: 366–369.

    Article  CAS  PubMed  Google Scholar 

  • Hann SR and Eiseman RN. . 1984 Mol. Cell. Biol. 4: 2486–2497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ioannidis P, Havredaki M, Courtis N and Trangas T. . 1996 Nucl. Acids Res. 24: 4969–4977.

  • Jackson RJ and Standart N. . 1990 Cell 62: 15–24.

    Article  CAS  PubMed  Google Scholar 

  • Jackson RJ, Hunt SL, Reynolds JE and Kaminski A. . 1995 Curr. Top. Microbiol. Immunol. 203: 1–29.

  • Jacobson A and Peltz SW. . 1996 Annu. Rev. Biochem. 65: 693–739.

    Article  CAS  PubMed  Google Scholar 

  • Kleene KC. . 1989 Development 106: 367–373.

  • Koromilas A, Lazaris-Karatzas A and Sonenberg N. . 1992 EMBO J. 11: 4153–4158.

  • Kovary K and Bravo R. . 1991 Mol. Cell. Biol. 11: 2451–2459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kozak M. . 1991 J. Cell. Biol. 115: 887–903.

  • Krumm A, Meulia T, Brunvand M and Groudine M. . 1992 Genes Dev. 6: 2201–2213.

  • Kruys V, Marinx O, Shaw G, Deschamps J and Huez G. . 1989 Science 245: 852–854.

    Article  CAS  PubMed  Google Scholar 

  • Kruys V, Wathelet MG and Huez GA. . 1988 Gene 72: 191–200.

    Article  CAS  PubMed  Google Scholar 

  • Lin J-X J and Vilcek J. . 1987 J. Biol. Chem. 262: 11908–11911.

  • Lorenzini EC and Scheffler IE. . 1997 Biochem. J. 326: 361–367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL and Randall RJ. . 1950 J. Biol. Chem. 193: 265–275.

  • Ma WJ, Chung S and Furneaux H. . 1997 Nucl. Acids Res. 25: 3564–3569.

  • Maciejewski-Lenoir D, Jirikowski GF, Sanna PP and Bloom FE. . 1993 Proc. Natl. Acad. Sci. USA 90: 1435–1439.

  • Marth JD, Overell RW, Meier KE, Krebs EG and Permutter RM. . 1988 Nature 332: 171–173.

    Article  CAS  PubMed  Google Scholar 

  • Munroe D and Jacobson A. . 1990 Mol. Cell. Biol. 10: 3441–3455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nabru C, Lafon I, Audigier S, Gensac M-C, Vagner S, Huez G and Prats A-C. . 1997 J. Biol. Chem. 272: 32061–32066.

    Article  CAS  PubMed  Google Scholar 

  • Paulin F, West MJ, Sullivan NF, Whitney RL, Lyne L and Willis AE. . 1996 Oncogene 13: 505–513.

  • Ranganathan G, Vu D and Kern PA. . 1997 J. Biol. Chem. 272: 2515–2519.

    Article  CAS  PubMed  Google Scholar 

  • Rao CD, Pech K, Robbins KC and Aaronson SA. . 1988 Mol. Cell. Biol. 8: 284–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross J. . 1995 Microbiol. Rev. 59: 423–450.

  • Sachs A. . 1990 Curr. Opin. Cell. Biol. 2: 1092–1098.

  • Sachs A and Wahle E. . 1993 J. Biol. Chem. 268: 22955–22958.

  • Sachs A, Sarnow P and Hentze M. . 1997 Cell 89: 831–838.

    Article  CAS  PubMed  Google Scholar 

  • Salles FJ, Lieberfarb ME, Wreden C, Gergen JP and Strickland S. . 1994 Science 266: 1996–1999.

    Article  CAS  PubMed  Google Scholar 

  • Shaw G and Kamen R. . 1986 Cell 46: 659–667.

    Article  CAS  PubMed  Google Scholar 

  • Sheets MD, Fox CA, Hunt T, Van De Wounde G and Wickens M. . 1994 Genes Dev. 8: 926–938.

  • Sheets MD, Wu M and Wickens M. . 1995 Nature 374: 511–516.

    Article  CAS  PubMed  Google Scholar 

  • Spotts GD and Hann SR. . 1990 Mol. Cell. Biol. 10: 3952–3964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stoeckle M and Guan L. . 1993 BioTeckniques 15: 230–231.

  • Stoneley M, Paulin F, Le Quesne J, Chappell S and Willis AE. . 1998 Oncogene 16: 423–428.

    Article  CAS  PubMed  Google Scholar 

  • Swartwout SG and Kinninburgh AJ. . 1989 Mol. Cell. Biol. 9: 288–295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tarun SZ and Sachs AB. . 1995 Genes Dev. 9: 2997–3007.

  • Thompson CB, Challoner PB, Neiman PE and Groudine M. . 1985 Nature 314: 363–366.

    Article  CAS  PubMed  Google Scholar 

  • Yang Q, McDermott PJ, Duzic E, Pleij WA, Sherlock JD and Lanier SM. . 1997 J. Biol. Chem. 272: 15466–15473.

    Article  CAS  PubMed  Google Scholar 

  • Zeevi M, Nevins JR and Darnell Jr JE. . 1982 Mol. Cell. Biol. 2: 517–525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zubiaga AM, Belasco JG and Greenberg ME. . 1995 Mol. Cell. Biol. 15: 2219–2230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Professor J Vilcek for providing the FS-4 human cell line. This work was partially supported by a grant from the Greek Ministry of Health to TT.

Author information

Authors and Affiliations

  1. Papanikolaou Research Center of Oncology, St Savvas Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    Panayotis Ioannidis, Nelly Courtis, Chris M Tsiapalis & Theoni Trangas

  2. NCSR-Democritos, Athens, Greece

    Panayotis Ioannidis & Maria Havredaki

  3. Oncology Unit, Athens General Hospital, Athens, Greece

    Emmanuel Michailakis

Authors
  1. Panayotis Ioannidis
    View author publications

    Search author on:PubMed Google Scholar

  2. Nelly Courtis
    View author publications

    Search author on:PubMed Google Scholar

  3. Maria Havredaki
    View author publications

    Search author on:PubMed Google Scholar

  4. Emmanuel Michailakis
    View author publications

    Search author on:PubMed Google Scholar

  5. Chris M Tsiapalis
    View author publications

    Search author on:PubMed Google Scholar

  6. Theoni Trangas
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ioannidis, P., Courtis, N., Havredaki, M. et al. The polyadenylation inhibitor cordycepin (3′dA) causes a decline in c-MYC mRNA levels without affecting c-MYC protein levels. Oncogene 18, 117–125 (1999). https://doi.org/10.1038/sj.onc.1202255

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1202255

Keywords

This article is cited by

Search

Advanced search

Quick links