Abstract
A general pathway of mRNA turnover has been described for yeast in which the 3' poly(A) tail is first deadenylated to an oligo(A) length, leading to decapping and subsequent 5'-3' exonucleolytic decay. The unstable MFA2 mRNA and the stable PGK1 mRNAs both decay through this pathway, albeit at different rates of deadenylation and decapping. To determine the regions of the mRNAs that are responsible for these differences, we examined the decay of chimeric mRNAs derived from the 5' untranslated, coding, and 3' untranslated regions of these two mRNAs. These experiments have led to the identification of the features of these mRNAs that lead to their different stabilities. The MFA2 mRNA is unstable solely because its 3' UTR promotes the rates of deadenylation and decapping; all other features of this mRNA are neutral with respect to mRNA decay rates. The PGK1 mRNA is stable because the sequence context of the PGK1 translation start codon and the coding region function together to stabilize the transcript, whereas the PGK13' UTR is neutral with respect to decay. Importantly, changes in the PGK1 start codon context that destabilized the transcript also reduced its translational efficiency. This observation suggests that the nature of the translation initiation complex modulates the rates of mRNA decapping and decay.
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- Anderson J. S., Parker R. P. The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex. EMBO J. 1998 Mar 2;17(5):1497–1506. doi: 10.1093/emboj/17.5.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atkin A. L., Altamura N., Leeds P., Culbertson M. R. The majority of yeast UPF1 co-localizes with polyribosomes in the cytoplasm. Mol Biol Cell. 1995 May;6(5):611–625. doi: 10.1091/mbc.6.5.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baim S. B., Pietras D. F., Eustice D. C., Sherman F. A mutation allowing an mRNA secondary structure diminishes translation of Saccharomyces cerevisiae iso-1-cytochrome c. Mol Cell Biol. 1985 Aug;5(8):1839–1846. doi: 10.1128/mcb.5.8.1839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beelman C. A., Parker R. Degradation of mRNA in eukaryotes. Cell. 1995 Apr 21;81(2):179–183. doi: 10.1016/0092-8674(95)90326-7. [DOI] [PubMed] [Google Scholar]
- Beelman C. A., Parker R. Differential effects of translational inhibition in cis and in trans on the decay of the unstable yeast MFA2 mRNA. J Biol Chem. 1994 Apr 1;269(13):9687–9692. [PubMed] [Google Scholar]
- Beelman C. A., Stevens A., Caponigro G., LaGrandeur T. E., Hatfield L., Fortner D. M., Parker R. An essential component of the decapping enzyme required for normal rates of mRNA turnover. Nature. 1996 Aug 15;382(6592):642–646. doi: 10.1038/382642a0. [DOI] [PubMed] [Google Scholar]
- Brown B. D., Zipkin I. D., Harland R. M. Sequence-specific endonucleolytic cleavage and protection of mRNA in Xenopus and Drosophila. Genes Dev. 1993 Aug;7(8):1620–1631. doi: 10.1101/gad.7.8.1620. [DOI] [PubMed] [Google Scholar]
- Caponigro G., Muhlrad D., Parker R. A small segment of the MAT alpha 1 transcript promotes mRNA decay in Saccharomyces cerevisiae: a stimulatory role for rare codons. Mol Cell Biol. 1993 Sep;13(9):5141–5148. doi: 10.1128/mcb.13.9.5141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caponigro G., Parker R. Mechanisms and control of mRNA turnover in Saccharomyces cerevisiae. Microbiol Rev. 1996 Mar;60(1):233–249. doi: 10.1128/mr.60.1.233-249.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cereghino G. P., Atencio D. P., Saghbini M., Beiner J., Scheffler I. E. Glucose-dependent turnover of the mRNAs encoding succinate dehydrogenase peptides in Saccharomyces cerevisiae: sequence elements in the 5' untranslated region of the Ip mRNA play a dominant role. Mol Biol Cell. 1995 Sep;6(9):1125–1143. doi: 10.1091/mbc.6.9.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cigan A. M., Pabich E. K., Donahue T. F. Mutational analysis of the HIS4 translational initiator region in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Jul;8(7):2964–2975. doi: 10.1128/mcb.8.7.2964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Decker C. J., Parker R. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev. 1993 Aug;7(8):1632–1643. doi: 10.1101/gad.7.8.1632. [DOI] [PubMed] [Google Scholar]
- Felici F., Cesareni G., Hughes J. M. The most abundant small cytoplasmic RNA of Saccharomyces cerevisiae has an important function required for normal cell growth. Mol Cell Biol. 1989 Aug;9(8):3260–3268. doi: 10.1128/mcb.9.8.3260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gera J. F., Baker E. J. Deadenylation-dependent and -independent decay pathways for alpha1-tubulin mRNA in Chlamydomonas reinhardtii. Mol Cell Biol. 1998 Mar;18(3):1498–1505. doi: 10.1128/mcb.18.3.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonzalez C. I., Martin C. E. Fatty acid-responsive control of mRNA stability. Unsaturated fatty acid-induced degradation of the Saccharomyces OLE1 transcript. J Biol Chem. 1996 Oct 18;271(42):25801–25809. doi: 10.1074/jbc.271.42.25801. [DOI] [PubMed] [Google Scholar]
- Heaton B., Decker C., Muhlrad D., Donahue J., Jacobson A., Parker R. Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay. Nucleic Acids Res. 1992 Oct 25;20(20):5365–5373. doi: 10.1093/nar/20.20.5365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herrick D., Parker R., Jacobson A. Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2269–2284. doi: 10.1128/mcb.10.5.2269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsu C. L., Stevens A. Yeast cells lacking 5'-->3' exoribonuclease 1 contain mRNA species that are poly(A) deficient and partially lack the 5' cap structure. Mol Cell Biol. 1993 Aug;13(8):4826–4835. doi: 10.1128/mcb.13.8.4826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobson A., Peltz S. W. Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem. 1996;65:693–739. doi: 10.1146/annurev.bi.65.070196.003401. [DOI] [PubMed] [Google Scholar]
- Kruys V., Huez G. Translational control of cytokine expression by 3' UA-rich sequences. Biochimie. 1994;76(9):862–866. doi: 10.1016/0300-9084(94)90188-0. [DOI] [PubMed] [Google Scholar]
- Muhlrad D., Decker C. J., Parker R. Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript. Genes Dev. 1994 Apr 1;8(7):855–866. doi: 10.1101/gad.8.7.855. [DOI] [PubMed] [Google Scholar]
- Muhlrad D., Decker C. J., Parker R. Turnover mechanisms of the stable yeast PGK1 mRNA. Mol Cell Biol. 1995 Apr;15(4):2145–2156. doi: 10.1128/mcb.15.4.2145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muhlrad D., Parker R. Mutations affecting stability and deadenylation of the yeast MFA2 transcript. Genes Dev. 1992 Nov;6(11):2100–2111. doi: 10.1101/gad.6.11.2100. [DOI] [PubMed] [Google Scholar]
- Muhlrad D., Parker R. Premature translational termination triggers mRNA decapping. Nature. 1994 Aug 18;370(6490):578–581. doi: 10.1038/370578a0. [DOI] [PubMed] [Google Scholar]
- Nielsen F. C., Christiansen J. Endonucleolysis in the turnover of insulin-like growth factor II mRNA. J Biol Chem. 1992 Sep 25;267(27):19404–19411. [PubMed] [Google Scholar]
- Peltz S. W., Donahue J. L., Jacobson A. A mutation in the tRNA nucleotidyltransferase gene promotes stabilization of mRNAs in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Dec;12(12):5778–5784. doi: 10.1128/mcb.12.12.5778. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierrat B., Lacroute F., Losson R. The 5' untranslated region of the PPR1 regulatory gene dictates rapid mRNA decay in yeast. Gene. 1993 Sep 6;131(1):43–51. doi: 10.1016/0378-1119(93)90667-r. [DOI] [PubMed] [Google Scholar]
- Presutti C., Villa T., Hall D., Pertica C., Bozzoni I. Identification of the cis-elements mediating the autogenous control of ribosomal protein L2 mRNA stability in yeast. EMBO J. 1995 Aug 15;14(16):4022–4030. doi: 10.1002/j.1460-2075.1995.tb00073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross J. mRNA stability in mammalian cells. Microbiol Rev. 1995 Sep;59(3):423–450. doi: 10.1128/mr.59.3.423-450.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yun D. F., Laz T. M., Clements J. M., Sherman F. mRNA sequences influencing translation and the selection of AUG initiator codons in the yeast Saccharomyces cerevisiae. Mol Microbiol. 1996 Mar;19(6):1225–1239. doi: 10.1111/j.1365-2958.1996.tb02468.x. [DOI] [PubMed] [Google Scholar]