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. 1990 Dec;10(12):6132–6140. doi: 10.1128/mcb.10.12.6132

Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation.

I A Laird-Offringa 1, C L de Wit 1, P Elfferich 1, A J van der Eb 1
PMCID: PMC362888  PMID: 1701014

Abstract

The highly unstable c-myc mRNA has been shown to be stabilized in cells treated with protein synthesis inhibitors. We have studied this phenomenon in an effort to gain more insight into the degradation pathway of this mRNA. Our results indicate that the stabilization of c-myc mRNA in the absence of translation can be fully explained by the inhibition of translation-dependent poly(A) tail shortening. This view is based on the following observations. First, the normally rapid shortening of the c-myc poly(A) tail was slowed down by a translation block. Second, c-myc messengers which carry a short poly(A) tail, as a result of prolonged actinomycin D or 3'-deoxyadenosine treatment, were not stabilized by the inhibition of translation. We propose that c-myc mRNA degradation proceeds in at least two steps. The first step is the shortening of long poly(A) tails. This step requires ongoing translation and thus is responsible for the delay in mRNA degradation observed in the presence of protein synthesis inhibitors. The second step involves rapid degradation of the body of the mRNA, possibly preceded by the removal of the short remainder of the poly(A) tail. This last step is independent of translation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams J. M., Gerondakis S., Webb E., Corcoran L. M., Cory S. Cellular myc oncogene is altered by chromosome translocation to an immunoglobulin locus in murine plasmacytomas and is rearranged similarly in human Burkitt lymphomas. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1982–1986. doi: 10.1073/pnas.80.7.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandyopadhyay R., Coutts M., Krowczynska A., Brawerman G. Nuclease activity associated with mammalian mRNA in its native state: possible basis for selectivity in mRNA decay. Mol Cell Biol. 1990 May;10(5):2060–2069. doi: 10.1128/mcb.10.5.2060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brewer G., Ross J. Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system. Mol Cell Biol. 1988 Apr;8(4):1697–1708. doi: 10.1128/mcb.8.4.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brewer G., Ross J. Regulation of c-myc mRNA stability in vitro by a labile destabilizer with an essential nucleic acid component. Mol Cell Biol. 1989 May;9(5):1996–2006. doi: 10.1128/mcb.9.5.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cole M. D. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. [DOI] [PubMed] [Google Scholar]
  6. Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fort P., Rech J., Vie A., Piechaczyk M., Bonnieu A., Jeanteur P., Blanchard J. M. Regulation of c-fos gene expression in hamster fibroblasts: initiation and elongation of transcription and mRNA degradation. Nucleic Acids Res. 1987 Jul 24;15(14):5657–5667. doi: 10.1093/nar/15.14.5657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gay D. A., Sisodia S. S., Cleveland D. W. Autoregulatory control of beta-tubulin mRNA stability is linked to translation elongation. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5763–5767. doi: 10.1073/pnas.86.15.5763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graves R. A., Pandey N. B., Chodchoy N., Marzluff W. F. Translation is required for regulation of histone mRNA degradation. Cell. 1987 Feb 27;48(4):615–626. doi: 10.1016/0092-8674(87)90240-6. [DOI] [PubMed] [Google Scholar]
  11. Hann S. R., Eisenman R. N. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol. 1984 Nov;4(11):2486–2497. doi: 10.1128/mcb.4.11.2486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones T. R., Cole M. D. Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. Mol Cell Biol. 1987 Dec;7(12):4513–4521. doi: 10.1128/mcb.7.12.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laird-Offringa I. A., Elfferich P., Knaken H. J., de Ruiter J., van der Eb A. J. Analysis of polyadenylation site usage of the c-myc oncogene. Nucleic Acids Res. 1989 Aug 25;17(16):6499–6514. doi: 10.1093/nar/17.16.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
  15. Maderious A., Chen-Kiang S. Pausing and premature termination of human RNA polymerase II during transcription of adenovirus in vivo and in vitro. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5931–5935. doi: 10.1073/pnas.81.19.5931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mercer J. F., Wake S. A. An analysis of the rate of metallothionein mRNA poly(A)-shortening using RNA blot hybridization. Nucleic Acids Res. 1985 Nov 25;13(22):7929–7943. doi: 10.1093/nar/13.22.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pachter J. S., Yen T. J., Cleveland D. W. Autoregulation of tubulin expression is achieved through specific degradation of polysomal tubulin mRNAs. Cell. 1987 Oct 23;51(2):283–292. doi: 10.1016/0092-8674(87)90155-3. [DOI] [PubMed] [Google Scholar]
  18. Piechaczyk M., Yang J. Q., Blanchard J. M., Jeanteur P., Marcu K. B. Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell. 1985 Sep;42(2):589–597. doi: 10.1016/0092-8674(85)90116-3. [DOI] [PubMed] [Google Scholar]
  19. Rahmsdorf H. J., Schönthal A., Angel P., Litfin M., Rüther U., Herrlich P. Posttranscriptional regulation of c-fos mRNA expression. Nucleic Acids Res. 1987 Feb 25;15(4):1643–1659. doi: 10.1093/nar/15.4.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ross J., Kobs G., Brewer G., Peltz S. W. Properties of the exonuclease activity that degrades H4 histone mRNA. J Biol Chem. 1987 Jul 5;262(19):9374–9381. [PubMed] [Google Scholar]
  21. Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
  22. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  23. Shuman S., Moss B. Vaccinia virus poly(A) polymerase. Specificity for nucleotides and nucleotide analogs. J Biol Chem. 1988 Jun 15;263(17):8405–8412. [PubMed] [Google Scholar]
  24. Stimac E., Groppi V. E., Jr, Coffino P. Inhibition of protein synthesis stabilizes histone mRNA. Mol Cell Biol. 1984 Oct;4(10):2082–2090. doi: 10.1128/mcb.4.10.2082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Swartwout S. G., Kinniburgh A. J. c-myc RNA degradation in growing and differentiating cells: possible alternate pathways. Mol Cell Biol. 1989 Jan;9(1):288–295. doi: 10.1128/mcb.9.1.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Expression of the c-myb proto-oncogene during cellular proliferation. 1986 Jan 30-Feb 5Nature. 319(6052):374–380. doi: 10.1038/319374a0. [DOI] [PubMed] [Google Scholar]
  27. Wilson T., Treisman R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences. Nature. 1988 Nov 24;336(6197):396–399. doi: 10.1038/336396a0. [DOI] [PubMed] [Google Scholar]
  28. Zandomeni R., Mittleman B., Bunick D., Ackerman S., Weinmann R. Mechanism of action of dichloro-beta-D-ribofuranosylbenzimidazole: effect on in vitro transcription. Proc Natl Acad Sci U S A. 1982 May;79(10):3167–3170. doi: 10.1073/pnas.79.10.3167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zeevi M., Nevins J. R., Darnell J. E., Jr Newly formed mRNA lacking polyadenylic acid enters the cytoplasm and the polyribosomes but has a shorter half-life in the absence of polyadenylic acid. Mol Cell Biol. 1982 May;2(5):517–525. doi: 10.1128/mcb.2.5.517. [DOI] [PMC free article] [PubMed] [Google Scholar]

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