Abstract
In yeast, many genes encoding amino acid biosynthetic enzymes are subject to a common regulatory system called the general control of amino acid biosynthesis. The product of the regulatory gene GCN4 is required for an increase in transcription of general control-regulated genes when yeast are grown under amino acid-starvation conditions. In this report, we show that the expression of the GCN4 gene is regulated at the translational level: the efficiency of translation of the GCN4 mRNA is dramatically increased during growth under amino acid-starvation conditions. The complete nucleotide sequence of the GCN4 gene, presented here, reveals the existence of an unusually long 5' untranslated region in the corresponding mRNA. In vivo analysis of the effects of a deletion in this 5' leader has enabled us to define a region required for the translational regulation of the GCN4 mRNA.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Casadaban M. J., Chou J., Cohen S. N. In vitro gene fusions that join an enzymatically active beta-galactosidase segment to amino-terminal fragments of exogenous proteins: Escherichia coli plasmid vectors for the detection and cloning of translational initiation signals. J Bacteriol. 1980 Aug;143(2):971–980. doi: 10.1128/jb.143.2.971-980.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donahue T. F., Daves R. S., Lucchini G., Fink G. R. A short nucleotide sequence required for regulation of HIS4 by the general control system of yeast. Cell. 1983 Jan;32(1):89–98. doi: 10.1016/0092-8674(83)90499-3. [DOI] [PubMed] [Google Scholar]
- Edwards J. C., Osinga K. A., Christianson T., Hensgens L. A., Janssens P. M., Rabinowitz M., Tabak H. F. Initiation of transcription of the yeast mitochondrial gene coding for ATPase subunit 9. Nucleic Acids Res. 1983 Dec 10;11(23):8269–8282. doi: 10.1093/nar/11.23.8269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Griffin-Shea R., Thireos G., Kafatos F. C., Petri W. H., Villa-Komaroff L. Chorion cDNA clones of D. melanogaster and their use in studies of sequence homology and chromosomal location of chorion genes. Cell. 1980 Apr;19(4):915–922. doi: 10.1016/0092-8674(80)90083-5. [DOI] [PubMed] [Google Scholar]
- Guo L. H., Wu R. Exonuclease III: use for DNA sequence analysis and in specific deletions of nucleotides. Methods Enzymol. 1983;100:60–96. doi: 10.1016/0076-6879(83)00046-4. [DOI] [PubMed] [Google Scholar]
- Henikoff S., Kelly J. D., Cohen E. H. Transcription terminates in yeast distal to a control sequence. Cell. 1983 Jun;33(2):607–614. doi: 10.1016/0092-8674(83)90441-5. [DOI] [PubMed] [Google Scholar]
- Hinnebusch A. G., Fink G. R. Positive regulation in the general amino acid control of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374–5378. doi: 10.1073/pnas.80.17.5374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinnebusch A. G., Fink G. R. Repeated DNA sequences upstream from HIS1 also occur at several other co-regulated genes in Saccharomyces cerevisiae. J Biol Chem. 1983 Apr 25;258(8):5238–5247. [PubMed] [Google Scholar]
- Klopotowski T., Wiater A. Synergism of aminotriazole and phosphate on the inhibition of yeast imidazole glycerol phosphate dehydratase. Arch Biochem Biophys. 1965 Dec;112(3):562–566. doi: 10.1016/0003-9861(65)90096-2. [DOI] [PubMed] [Google Scholar]
- Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. doi: 10.1128/mr.47.1.1-45.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak M. Selection of initiation sites by eucaryotic ribosomes: effect of inserting AUG triplets upstream from the coding sequence for preproinsulin. Nucleic Acids Res. 1984 May 11;12(9):3873–3893. doi: 10.1093/nar/12.9.3873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Legerski R. J., Hodnett J. L., Gray H. B., Jr Extracellular nucleases of pseudomonas BAL 31. III. Use of the double-strand deoxyriboexonuclease activity as the basis of a convenient method for the mapping of fragments of DNA produced by cleavage with restriction enzymes. Nucleic Acids Res. 1978 May;5(5):1445–1464. doi: 10.1093/nar/5.5.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu C. C., Simonsen C. C., Levinson A. D. Initiation of translation at internal AUG codons in mammalian cells. Nature. 1984 May 3;309(5963):82–85. doi: 10.1038/309082a0. [DOI] [PubMed] [Google Scholar]
- Losson R., Fuchs R. P., Lacroute F. In vivo transcription of a eukaryotic regulatory gene. EMBO J. 1983;2(12):2179–2184. doi: 10.1002/j.1460-2075.1983.tb01720.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Messenguy F., Dubois E. Participation of transcriptional and post-transcriptional regulatory mechanisms in the control of arginine metabolism in yeast. Mol Gen Genet. 1983;189(1):148–156. doi: 10.1007/BF00326068. [DOI] [PubMed] [Google Scholar]
- Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
- Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
- Penn M. D., Galgoci B., Greer H. Identification of AAS genes and their regulatory role in general control of amino acid biosynthesis in yeast. Proc Natl Acad Sci U S A. 1983 May;80(9):2704–2708. doi: 10.1073/pnas.80.9.2704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Penn M. D., Thireos G., Greer H. Temporal analysis of general control of amino acid biosynthesis in Saccharomyces cerevisiae: role of positive regulatory genes in initiation and maintenance of mRNA derepression. Mol Cell Biol. 1984 Mar;4(3):520–528. doi: 10.1128/mcb.4.3.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rose M., Casadaban M. J., Botstein D. Yeast genes fused to beta-galactosidase in Escherichia coli can be expressed normally in yeast. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2460–2464. doi: 10.1073/pnas.78.4.2460. [DOI] [PMC free article] [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]
- Schmidt O., Mao J., Ogden R., Beckmann J., Sakano H., Abelson J., Söll D. Dimeric tRNA precursors in yeast. Nature. 1980 Oct 23;287(5784):750–752. doi: 10.1038/287750a0. [DOI] [PubMed] [Google Scholar]
- Schürch A., Miozzari J., Hütter R. Regulation of tryptophan biosynthesis in Saccharomyces cerevisiae: mode of action of 5-methyl-tryptophan and 5-methyl-tryptophan-sensitive mutants. J Bacteriol. 1974 Mar;117(3):1131–1140. doi: 10.1128/jb.117.3.1131-1140.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silverman S. J., Rose M., Botstein D., Fink G. R. Regulation of HIS4-lacZ fusions in Saccharomyces cerevisiae. Mol Cell Biol. 1982 Oct;2(10):1212–1219. doi: 10.1128/mcb.2.10.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Storti R. V., Scott M. P., Rich A., Pardue M. L. Translational control of protein synthesis in response to heat shock in D. melanogaster cells. Cell. 1980 Dec;22(3):825–834. doi: 10.1016/0092-8674(80)90559-0. [DOI] [PubMed] [Google Scholar]
- Struhl K., Davis R. W. Promotor mutants of the yeast his3 gene. J Mol Biol. 1981 Nov 5;152(3):553–568. doi: 10.1016/0022-2836(81)90268-0. [DOI] [PubMed] [Google Scholar]
- Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
- Wolfner M., Yep D., Messenguy F., Fink G. R. Integration of amino acid biosynthesis into the cell cycle of Saccharomyces cerevisiae. J Mol Biol. 1975 Aug 5;96(2):273–290. doi: 10.1016/0022-2836(75)90348-4. [DOI] [PubMed] [Google Scholar]
- Woodland H. The translational control phase of early development. Biosci Rep. 1982 Jul;2(7):471–491. doi: 10.1007/BF01115246. [DOI] [PubMed] [Google Scholar]
- Yates J. L., Dean D., Strycharz W. A., Nomura M. E. coli ribosomal protein L10 inhibits translation of L10 and L7/L12 mRNAs by acting at a single site. Nature. 1981 Nov 12;294(5837):190–192. doi: 10.1038/294190a0. [DOI] [PubMed] [Google Scholar]
- Zalkin H., Yanofsky C. Yeast gene TRP5: structure, function, regulation. J Biol Chem. 1982 Feb 10;257(3):1491–1500. [PubMed] [Google Scholar]
- Zaret K. S., Sherman F. DNA sequence required for efficient transcription termination in yeast. Cell. 1982 Mar;28(3):563–573. doi: 10.1016/0092-8674(82)90211-2. [DOI] [PubMed] [Google Scholar]