Abstract
The c-fos proto-oncogene provides a good system to study the processes underlying messenger RNA degradation. After growth factor stimulation of susceptible cells, the c-fos transcription rate transiently increases from a low basal level by as much as 50-fold1, producing a large amount of exceedingly unstable c-fos mRNA that is rapidly degraded1–3. Here, we investigate the c-fos mRNA degradation process, and find that: (1) ongoing translation of the c-fos mRNA itself is required for its degradation; (2) after synthesis, the mRNA poly(A) tail is rapidly removed, in a translation-dependent manner, leading to accumulation of apparently de-adenylated RNA; (3) deletion or replacement of an AU-rich sequence at the mRNA 3′ end significantly stabilizes the mRNA; (4) deletion of the 3′ AU-rich sequences dramatically slows the poly(A) shortening rate. These results suggest that the 3′ AU-rich sequences act to destabilize the mRNA by directing rapid removal of the mRNA poly(A) tract.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Greenberg, M. E. & Ziff, E. B. Nature 311, 433–438 (1984).
Kruijer, W., Cooper, J. A., Hunter, T. & Verma, I. M. Nature 312, 711–716 (1984).
Muller, R., Bravo, R., Burckhardt, J. & Curran, T. Nature 312, 716–720 (1984).
Treisman, R. H. Cell 42, 889–902 (1985).
Mitchell, R. L., Henning-Chubb, C., Huberman, E. & Verma, I. M. Cell 45, 567–574 (1986).
Brewer, G. & Ross, J. Molec. cell. Biol. 8, 1697–1708 (1988).
Fort, P. et al. Nucleic. Acids Res. 15, 5567–5667 (1987).
Rahmsdorf, H-J. et al. Nucleic. Acids Res. 15, 1643–1649 (1987).
Miller, A. D., Curran, T. & Verma, I. M. Cell 36, 51–60 (1984).
Meijlink, F. & Verma, I. M. Proc. natn. Acad. Sci. U.S.A. 82, 4987–4991 (1985).
Shaw, G. & Kamen, R. I. Cell 46, 659–667 (1986).
Graves, R. F., Pandey, N. B., Chodchoy, N. & Marzluff, W. F. Cell 48, 615–626 (1987).
Sussman, M. Nature 225, 1245–1246 (1970).
Sheiness, D., Puckett, L. & Darnell, J. E. Proc. natn. Acad. Sci. U.S.A. 72, 1077–1081 (1975).
Sheiness, D. & Darnell, J. E. Nature 241, 265–268 (1973).
Merkel, C. G., Kwan, S-P. & Lingrel, J. B. J. biol. Chem. 250, 3725–3728 (1975).
Medford, R. M., Wydro, R. M., Nguyen, H. T. & Nadal-Ginard, B. Proc. natn. Acad. Sci. U.S.A. 77, 5749–5753 (1980).
Mercer, J. F. B. & Wake, S. A. Nucleic Acids Res. 13, 7929–7943 (1985).
Wilson, M. C., Sawicki, S. G., White, P. A. & Darnell, J. E. J. molec. Biol. 126, 23–36 (1978).
Zeevi, M., Nevins, J. & Darnell, J. E. Molec. cell. Biol. 7, 517–525 (1982).
Paek, I. & Axel, R. Molec. cell. Biol. 7, 1496–1507 (1987).
Deshpande, A. K., Chatterjee, B. & Roy, A. K. J. biol. Chem. 254, 8937–8942 (1979).
Muschel, R., Khoury, G. & Reid, L. M. Molec. cell. Biol. 6, 337–341 (1986).
Marbaix, G. et al. Proc. natn. Acad. Sci. U.S.A. 72, 3065–3067 (1975).
Huez, G. et al. Eur. J. Biochem. 59, 589–592 (1975).
Dani, C. et al. Proc. natn. Acad. Sci. U.S.A. 81, 7046–7050 (1984).
Lau, L. F. & Nathans, D. Proc. natn. Acad. Sci. U.S.A. 84, 1182–1186 (1987).
Almendral, J. M. et al. Molec. cell. Biol. 8, 2140–2148 (1988).
Van Beveren, C., van Straaten, F., Curran, T., Muller, R. & Verma, I. M. Cell 32, 1241–1255 (1983).
Van Straaten, F., van Beveren, C., Curran, T. & Verma, I. M. Proc. natn. Acad. Sci. U.S.A. 80, 3183–3187 (1983).
Southern, P. & Berg, P. J. molec. appl. Genet. 1, 327–337 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wilson, T., Treisman, R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3′ AU-rich sequences. Nature 336, 396–399 (1988). https://doi.org/10.1038/336396a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/336396a0
This article is cited by
-
Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression
Nature Reviews Molecular Cell Biology (2022)
-
Temporal evolution of cortical ensembles promoting remote memory retrieval
Nature Neuroscience (2019)
-
Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization
Scientific Reports (2019)
-
Lack of effective translational regulation of PLD expression and exosome biogenesis in triple-negative breast cancer cells
Cancer and Metastasis Reviews (2018)
-
Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation
Cell Research (2014)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.