Abstract
We reported previously that early meiotic transcripts are highly unstable. These mRNAs exhibit half-lives of approximately 3 min when expressed during vegetative growth in glucose medium and are stabilized twofold during sporulation in acetate medium. Two genes, UME2 and UME5, that regulate the stability of meiosis-specific transcripts have been identified. The wild-type UME5 gene, which has been analyzed in detail, decreases the stability of all meiotic mRNAs tested approximately twofold when expressed during vegetative growth but has no effect on the half-lives of a number of vegetative mRNAs examined. The UME5 gene is dispensable for mitotic and meiotic development. Cells in which the entire UME5 gene has been deleted are viable, although the generation time is slightly longer and sporulation is less efficient. The UME5 transcript is constitutively expressed, and its stability is not autoregulated. The UME5 gene encodes a predicted 63-kDa protein with homology to the family of CDC28 serine/threonine-specific protein kinases. The kinase activity appears to be central to the function of the UME5 protein, since alteration of a highly conserved amino acid in the kinase domain results in a phenotype identical to that of a ume5 deletion. Genetic epistasis studies suggest that the UME2 and UME5 gene products act in the same pathway to regulate meiotic transcript stability. This pathway is independent of deadenylation and translation, two factors known to be important in regulating mRNA turnover. Significantly, the UME5-mediated destabilization of meiotic mRNAs occurs in glucose- but not in acetate-containing medium. Thus, the UME5 gene appears to participate in a glucose signal transduction pathway governing message stability.
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- Aharon T., Schneider R. J. Selective destabilization of short-lived mRNAs with the granulocyte-macrophage colony-stimulating factor AU-rich 3' noncoding region is mediated by a cotranslational mechanism. Mol Cell Biol. 1993 Mar;13(3):1971–1980. doi: 10.1128/mcb.13.3.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
- Atcheson C. L., DiDomenico B., Frackman S., Esposito R. E., Elder R. T. Isolation, DNA sequence, and regulation of a meiosis-specific eukaryotic recombination gene. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8035–8039. doi: 10.1073/pnas.84.22.8035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker B. S., Carpenter A. T., Esposito M. S., Esposito R. E., Sandler L. The genetic control of meiosis. Annu Rev Genet. 1976;10:53–134. doi: 10.1146/annurev.ge.10.120176.000413. [DOI] [PubMed] [Google Scholar]
- Becker D. M., Guarente L. High-efficiency transformation of yeast by electroporation. Methods Enzymol. 1991;194:182–187. doi: 10.1016/0076-6879(91)94015-5. [DOI] [PubMed] [Google Scholar]
- Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
- Bowdish K. S., Mitchell A. P. Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2172–2181. doi: 10.1128/mcb.13.4.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Briza P., Breitenbach M., Ellinger A., Segall J. Isolation of two developmentally regulated genes involved in spore wall maturation in Saccharomyces cerevisiae. Genes Dev. 1990 Oct;4(10):1775–1789. doi: 10.1101/gad.4.10.1775. [DOI] [PubMed] [Google Scholar]
- Carlson M. Regulation of sugar utilization in Saccharomyces species. J Bacteriol. 1987 Nov;169(11):4873–4877. doi: 10.1128/jb.169.11.4873-4877.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casey J. L., Hentze M. W., Koeller D. M., Caughman S. W., Rouault T. A., Klausner R. D., Harford J. B. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science. 1988 May 13;240(4854):924–928. doi: 10.1126/science.2452485. [DOI] [PubMed] [Google Scholar]
- Celenza J. L., Carlson M. A yeast gene that is essential for release from glucose repression encodes a protein kinase. Science. 1986 Sep 12;233(4769):1175–1180. doi: 10.1126/science.3526554. [DOI] [PubMed] [Google Scholar]
- Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. doi: 10.1016/0378-1119(92)90454-w. [DOI] [PubMed] [Google Scholar]
- Dower W. J., Miller J. F., Ragsdale C. W. High efficiency transformation of E. coli by high voltage electroporation. Nucleic Acids Res. 1988 Jul 11;16(13):6127–6145. doi: 10.1093/nar/16.13.6127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elder R. T., Loh E. Y., Davis R. W. RNA from the yeast transposable element Ty1 has both ends in the direct repeats, a structure similar to retrovirus RNA. Proc Natl Acad Sci U S A. 1983 May;80(9):2432–2436. doi: 10.1073/pnas.80.9.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerring S. L., Connelly C., Hieter P. Positional mapping of genes by chromosome blotting and chromosome fragmentation. Methods Enzymol. 1991;194:57–77. doi: 10.1016/0076-6879(91)94007-y. [DOI] [PubMed] [Google Scholar]
- Gietz R. D., Sugino A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988 Dec 30;74(2):527–534. doi: 10.1016/0378-1119(88)90185-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Hahn S., Guarente L. Yeast HAP2 and HAP3: transcriptional activators in a heteromeric complex. Science. 1988 Apr 15;240(4850):317–321. doi: 10.1126/science.2832951. [DOI] [PubMed] [Google Scholar]
- Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
- Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [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]
- Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [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]
- Hollingsworth N. M., Goetsch L., Byers B. The HOP1 gene encodes a meiosis-specific component of yeast chromosomes. Cell. 1990 Apr 6;61(1):73–84. doi: 10.1016/0092-8674(90)90216-2. [DOI] [PubMed] [Google Scholar]
- Honigberg S. M., Conicella C., Espositio R. E. Commitment to meiosis in Saccharomyces cerevisiae: involvement of the SPO14 gene. Genetics. 1992 Apr;130(4):703–716. doi: 10.1093/genetics/130.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hwang S. P., Eisenberg M., Binder R., Shelness G. S., Williams D. L. Predicted structures of apolipoprotein II mRNA constrained by nuclease and dimethyl sulfate reactivity: stable secondary structures occur predominantly in local domains via intraexonic base pairing. J Biol Chem. 1989 May 15;264(14):8410–8418. [PubMed] [Google Scholar]
- Johnston M., Davis R. W. Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Aug;4(8):1440–1448. doi: 10.1128/mcb.4.8.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaback D. B., Feldberg L. R. Saccharomyces cerevisiae exhibits a sporulation-specific temporal pattern of transcript accumulation. Mol Cell Biol. 1985 Apr;5(4):751–761. doi: 10.1128/mcb.5.4.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamps M. P., Sefton B. M. Neither arginine nor histidine can carry out the function of lysine-295 in the ATP-binding site of p60src. Mol Cell Biol. 1986 Mar;6(3):751–757. doi: 10.1128/mcb.6.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kassir Y., Granot D., Simchen G. IME1, a positive regulator gene of meiosis in S. cerevisiae. Cell. 1988 Mar 25;52(6):853–862. doi: 10.1016/0092-8674(88)90427-8. [DOI] [PubMed] [Google Scholar]
- Lee M. G., Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. doi: 10.1038/327031a0. [DOI] [PubMed] [Google Scholar]
- Lombardo A., Cereghino G. P., Scheffler I. E. Control of mRNA turnover as a mechanism of glucose repression in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Jul;12(7):2941–2948. doi: 10.1128/mcb.12.7.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lörincz A. T., Reed S. I. Primary structure homology between the product of yeast cell division control gene CDC28 and vertebrate oncogenes. Nature. 1984 Jan 12;307(5947):183–185. doi: 10.1038/307183a0. [DOI] [PubMed] [Google Scholar]
- Malavasic M. J., Elder R. T. Complementary transcripts from two genes necessary for normal meiosis in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1990 Jun;10(6):2809–2819. doi: 10.1128/mcb.10.6.2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarroll R. M., Fangman W. L. Time of replication of yeast centromeres and telomeres. Cell. 1988 Aug 12;54(4):505–513. doi: 10.1016/0092-8674(88)90072-4. [DOI] [PubMed] [Google Scholar]
- McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minvielle-Sebastia L., Winsor B., Bonneaud N., Lacroute F. Mutations in the yeast RNA14 and RNA15 genes result in an abnormal mRNA decay rate; sequence analysis reveals an RNA-binding domain in the RNA15 protein. Mol Cell Biol. 1991 Jun;11(6):3075–3087. doi: 10.1128/mcb.11.6.3075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitchell A. P., Driscoll S. E., Smith H. E. Positive control of sporulation-specific genes by the IME1 and IME2 products in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2104–2110. doi: 10.1128/mcb.10.5.2104. [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]
- Müllner E. W., Kühn L. C. A stem-loop in the 3' untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell. 1988 Jun 3;53(5):815–825. doi: 10.1016/0092-8674(88)90098-0. [DOI] [PubMed] [Google Scholar]
- Nonet M., Scafe C., Sexton J., Young R. Eucaryotic RNA polymerase conditional mutant that rapidly ceases mRNA synthesis. Mol Cell Biol. 1987 May;7(5):1602–1611. doi: 10.1128/mcb.7.5.1602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Pandey N. B., Marzluff W. F. The stem-loop structure at the 3' end of histone mRNA is necessary and sufficient for regulation of histone mRNA stability. Mol Cell Biol. 1987 Dec;7(12):4557–4559. doi: 10.1128/mcb.7.12.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parker R., Herrick D., Peltz S. W., Jacobson A. Measurement of mRNA decay rates in Saccharomyces cerevisiae. Methods Enzymol. 1991;194:415–423. doi: 10.1016/0076-6879(91)94032-8. [DOI] [PubMed] [Google Scholar]
- Parker R., Jacobson A. Translation and a 42-nucleotide segment within the coding region of the mRNA encoded by the MAT alpha 1 gene are involved in promoting rapid mRNA decay in yeast. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2780–2784. doi: 10.1073/pnas.87.7.2780. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patschinsky T., Hunter T., Esch F. S., Cooper J. A., Sefton B. M. Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation. Proc Natl Acad Sci U S A. 1982 Feb;79(4):973–977. doi: 10.1073/pnas.79.4.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peltz S. W., Brewer G., Bernstein P., Hart P. A., Ross J. Regulation of mRNA turnover in eukaryotic cells. Crit Rev Eukaryot Gene Expr. 1991;1(2):99–126. [PubMed] [Google Scholar]
- Percival-Smith A., Segall J. Isolation of DNA sequences preferentially expressed during sporulation in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Jan;4(1):142–150. doi: 10.1128/mcb.4.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perkins D. D. Biochemical Mutants in the Smut Fungus Ustilago Maydis. Genetics. 1949 Sep;34(5):607–626. doi: 10.1093/genetics/34.5.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs A. B. Messenger RNA degradation in eukaryotes. Cell. 1993 Aug 13;74(3):413–421. doi: 10.1016/0092-8674(93)80043-e. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shah J. C., Clancy M. J. IME4, a gene that mediates MAT and nutritional control of meiosis in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Mar;12(3):1078–1086. doi: 10.1128/mcb.12.3.1078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharp P. M., Li W. H. The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987 Feb 11;15(3):1281–1295. doi: 10.1093/nar/15.3.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shyu A. B., Belasco J. G., Greenberg M. E. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev. 1991 Feb;5(2):221–231. doi: 10.1101/gad.5.2.221. [DOI] [PubMed] [Google Scholar]
- Simanis V., Nurse P. The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell. 1986 Apr 25;45(2):261–268. doi: 10.1016/0092-8674(86)90390-9. [DOI] [PubMed] [Google Scholar]
- Simchen G., Piñon R., Salts Y. Sporulation in Saccharomyces cerevisiae: premeiotic DNA synthesis, readiness and commitment. Exp Cell Res. 1972 Nov;75(1):207–218. doi: 10.1016/0014-4827(72)90538-1. [DOI] [PubMed] [Google Scholar]
- Smith H. E., Mitchell A. P. A transcriptional cascade governs entry into meiosis in Saccharomyces cerevisiae. Mol Cell Biol. 1989 May;9(5):2142–2152. doi: 10.1128/mcb.9.5.2142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strich R., Slater M. R., Esposito R. E. Identification of negative regulatory genes that govern the expression of early meiotic genes in yeast. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10018–10022. doi: 10.1073/pnas.86.24.10018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Surosky R. T., Esposito R. E. Early meiotic transcripts are highly unstable in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Sep;12(9):3948–3958. doi: 10.1128/mcb.12.9.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toh-e A., Tanaka K., Uesono Y., Wickner R. B. PHO85, a negative regulator of the PHO system, is a homolog of the protein kinase gene, CDC28, of Saccharomyces cerevisiae. Mol Gen Genet. 1988 Sep;214(1):162–164. doi: 10.1007/BF00340196. [DOI] [PubMed] [Google Scholar]
- Trumbly R. J. Glucose repression in the yeast Saccharomyces cerevisiae. Mol Microbiol. 1992 Jan;6(1):15–21. doi: 10.1111/j.1365-2958.1992.tb00832.x. [DOI] [PubMed] [Google Scholar]
- Tsai L. H., Harlow E., Meyerson M. Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature. 1991 Sep 12;353(6340):174–177. doi: 10.1038/353174a0. [DOI] [PubMed] [Google Scholar]
- Vidal M., Strich R., Esposito R. E., Gaber R. F. RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes. Mol Cell Biol. 1991 Dec;11(12):6306–6316. doi: 10.1128/mcb.11.12.6306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vreken P., Raué H. A. The rate-limiting step in yeast PGK1 mRNA degradation is an endonucleolytic cleavage in the 3'-terminal part of the coding region. Mol Cell Biol. 1992 Jul;12(7):2986–2996. doi: 10.1128/mcb.12.7.2986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang H. T., Frackman S., Kowalisyn J., Esposito R. E., Elder R. Developmental regulation of SPO13, a gene required for separation of homologous chromosomes at meiosis I. Mol Cell Biol. 1987 Apr;7(4):1425–1435. doi: 10.1128/mcb.7.4.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang H., Clark I., Nicholson P. R., Herskowitz I., Stillman D. J. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Mol Cell Biol. 1990 Nov;10(11):5927–5936. doi: 10.1128/mcb.10.11.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
- Yen T. J., Gay D. A., Pachter J. S., Cleveland D. W. Autoregulated changes in stability of polyribosome-bound beta-tubulin mRNAs are specified by the first 13 translated nucleotides. Mol Cell Biol. 1988 Mar;8(3):1224–1235. doi: 10.1128/mcb.8.3.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]