Identification of GCD14 and GCD15, Novel Genes Required for Translational Repression of GCN4 mRNA in Saccharomyces cerevisiae

Corresponding author: Mercedes Tamame, Instituto de Microbiología Bioquímica del C.S.I.C./Universidad de Salamanca, Edificio Departamental de Biología, Campus Miguel de Unamuno, 37007, Salamanca, Spain, tamame{at}gugu.usal.es (E-mail).

Communicating editor: A. P. MITCHELL

In Saccharomyces cerevisiae, expression of the transcriptional activator GCN4 increases at the translational level in response to starvation for an amino acid. The products of multiple GCD genes are required for efficient repression of GCN4 mRNA translation under nonstarvation conditions. The majority of the known GCD genes encode subunits of the general translation initiation factor eIF-2 or eIF-2B. To identify additional initiation factors in yeast, we characterized 65 spontaneously arising Gcd^- mutants. In addition to the mutations that were complemented by known GCD genes or by GCN3, we isolated mutant alleles of two new genes named GCD14 and GCD15. Recessive mutations in these two genes led to highly unregulated GCN4 expression and to derepressed transcription of genes in the histidine biosynthetic pathway under GCN4 control. The derepression of GCN4 expression in gcd14 and gcd15 mutants occurred with little or no increase in GCN4 mRNA levels, and it was dependent on upstream open reading frames (uORFs) in GCN4 mRNA that regulate its translation. We conclude that GCD14 and GCD15 are required for repression of GCN4 mRNA translation by the uORFs under conditions of amino acid sufficiency. The gcd14 and gcd15 mutations confer a slow-growth phenotype on nutrient-rich medium, and gcd15 mutations are lethal when combined with a mutation in gcd13. Like other known GCD genes, GCD14 and GCD15 are therefore probably required for general translation initiation in addition to their roles in GCN4-specific translational control.

This article has been cited by other articles:

				S. G. Ozanick, J. M. Bujnicki, D. S. Sem, and J. T. Anderson Conserved amino acids in each subunit of the heteroligomeric tRNA m1A58 Mtase from Saccharomyces cerevisiae contribute to tRNA binding Nucleic Acids Res., November 29, 2007; 35(20): 6808 - 6819. [Abstract] [Full Text] [PDF]

				P. Martin-Marcos, A. G. Hinnebusch, and M. Tamame Ribosomal Protein L33 Is Required for Ribosome Biogenesis, Subunit Joining, and Repression of GCN4 Translation Mol. Cell. Biol., September 1, 2007; 27(17): 5968 - 5985. [Abstract] [Full Text] [PDF]

				S. OZANICK, A. KRECIC, J. ANDERSLAND, and J. T. ANDERSON The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans RNA, August 1, 2005; 11(8): 1281 - 1290. [Abstract] [Full Text] [PDF]

				S. Kadaba, A. Krueger, T. Trice, A. M. Krecic, A. G. Hinnebusch, and J. Anderson Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae Genes & Dev., June 1, 2004; 18(11): 1227 - 1240. [Abstract] [Full Text] [PDF]

				E. Gomez and G. D. Pavitt Identification of Domains and Residues within the varepsilon Subunit of Eukaryotic Translation Initiation Factor 2B (eIF2Bvarepsilon ) Required for Guanine Nucleotide Exchange Reveals a Novel Activation Function Promoted by eIF2B Complex Formation Mol. Cell. Biol., June 1, 2000; 20(11): 3965 - 3976. [Abstract] [Full Text]

				H. Qiu, C. Hu, J. Anderson, G. R. Björk, S. Sarkar, A. K. Hopper, and A. G. Hinnebusch Defects in tRNA Processing and Nuclear Export Induce GCN4 Translation Independently of Phosphorylation of the alpha Subunit of Eukaryotic Translation Initiation Factor 2 Mol. Cell. Biol., April 1, 2000; 20(7): 2505 - 2516. [Abstract] [Full Text]

				O. Calvo, R. Cuesta, J. Anderson, N. Gutierrez, M. T. Garcia-Barrio, A. G. Hinnebusch, and M. Tamame GCD14p, a Repressor of GCN4 Translation, Cooperates with Gcd10p and Lhp1p in the Maturation of Initiator Methionyl-tRNA in Saccharomyces cerevisiae Mol. Cell. Biol., June 1, 1999; 19(6): 4167 - 4181. [Abstract] [Full Text] [PDF]

				A. Niewmierzycka and S. Clarke S-Adenosylmethionine-dependent Methylation in Saccharomyces cerevisiae. IDENTIFICATION OF A NOVEL PROTEIN ARGININE METHYLTRANSFERASE J. Biol. Chem., January 8, 1999; 274(2): 814 - 824. [Abstract] [Full Text] [PDF]

				J. Anderson, L. Phan, R. Cuesta, B. A. Carlson, M. Pak, K. Asano, G. R. Björk, M. Tamame, and A. G. Hinnebusch The essential Gcd10p-Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA Genes & Dev., December 1, 1998; 12(23): 3650 - 3662. [Abstract] [Full Text]

				K. J. Gerik, X. Li, A. Pautz, and P. M. J. Burgers Characterization of the Two Small Subunits of Saccharomyces cerevisiae DNA Polymerase delta J. Biol. Chem., July 31, 1998; 273(31): 19747 - 19755. [Abstract] [Full Text] [PDF]