Logo of embojLink to Publisher's site
EMBO J. 1999 Jun 1; 18(11): 3139–3152.
PMCID: PMC1171395

Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability.


A novel form of post-transcriptional control is described. The 5' untranslated region (5'UTR) of the Saccharomyces cerevisiae gene encoding the AP1-like transcription factor Yap2 contains two upstream open reading frames (uORF1 and uORF2). The YAP2-type of uORF functions as a cis-acting element that attenuates gene expression at the level of mRNA turnover via termination-dependent decay. Release of post-termination ribosomes from the YAP2 5'UTR causes accelerated decay which is largely independent of the termination modulator gene UPF1. Both of the YAP2 uORFs contribute to the destabilization effect. A G/C-rich stop codon context, which seems to promote ribosome release, allows an uORF to act as a transferable 5'UTR-destabilizing element. Moreover, termination-dependent destabilization is potentiated by stable secondary structure 3' of the uORF stop codon. The potentiation of uORF-mediated destabilization is eliminated if the secondary structure is located further downstream of the uORF, and is also influenced by a modulatory mechanism involving eIF2. Destabilization is therefore linked to the kinetics of acquisition of reinitiation-competence by post-termination ribosomes in the 5'UTR. Our data explain the destabilizing properties of YAP2-type uORFs and also support a more general model for the mode of action of other known uORFs, such as those in the GCN4 mRNA.

Full Text

The Full Text of this article is available as a PDF (472K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Abastado JP, Miller PF, Jackson BM, Hinnebusch AG. Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control. Mol Cell Biol. 1991 Jan;11(1):486–496. [PMC free article] [PubMed]
  • Bossier P, Fernandes L, Rocha D, Rodrigues-Pousada C. Overexpression of YAP2, coding for a new yAP protein, and YAP1 in Saccharomyces cerevisiae alleviates growth inhibition caused by 1,10-phenanthroline. J Biol Chem. 1993 Nov 5;268(31):23640–23645. [PubMed]
  • Buckingham RH, Grentzmann G, Kisselev L. Polypeptide chain release factors. Mol Microbiol. 1997 May;24(3):449–456. [PubMed]
  • Cavener DR, Ray SC. Eukaryotic start and stop translation sites. Nucleic Acids Res. 1991 Jun 25;19(12):3185–3192. [PMC free article] [PubMed]
  • Cui Y, Hagan KW, Zhang S, Peltz SW. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev. 1995 Feb 15;9(4):423–436. [PubMed]
  • Czaplinski K, Ruiz-Echevarria MJ, Paushkin SV, Han X, Weng Y, Perlick HA, Dietz HC, Ter-Avanesyan MD, Peltz SW. The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs. Genes Dev. 1998 Jun 1;12(11):1665–1677. [PMC free article] [PubMed]
  • Fernandes L, Rodrigues-Pousada C, Struhl K. Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions. Mol Cell Biol. 1997 Dec;17(12):6982–6993. [PMC free article] [PubMed]
  • Grant CM, Hinnebusch AG. Effect of sequence context at stop codons on efficiency of reinitiation in GCN4 translational control. Mol Cell Biol. 1994 Jan;14(1):606–618. [PMC free article] [PubMed]
  • Haase E, Servos J, Brendel M. Isolation and characterization of additional genes influencing resistance to various mutagens in the yeast Saccharomyces cerevisiae. Curr Genet. 1992 Apr;21(4-5):319–324. [PubMed]
  • Harshman KD, Moye-Rowley WS, Parker CS. Transcriptional activation by the SV40 AP-1 recognition element in yeast is mediated by a factor similar to AP-1 that is distinct from GCN4. Cell. 1988 Apr 22;53(2):321–330. [PubMed]
  • Hatfield L, Beelman CA, Stevens A, Parker R. Mutations in trans-acting factors affecting mRNA decapping in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Oct;16(10):5830–5838. [PMC free article] [PubMed]
  • Hennigan AN, Jacobson A. Functional mapping of the translation-dependent instability element of yeast MATalpha1 mRNA. Mol Cell Biol. 1996 Jul;16(7):3833–3843. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Hertle K, Haase E, Brendel M. The SNQ3 gene of Saccharomyces cerevisiae confers hyper-resistance to several functionally unrelated chemicals. Curr Genet. 1991 Jun;19(6):429–433. [PubMed]
  • Hinnebusch AG. Evidence for translational regulation of the activator of general amino acid control in yeast. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442–6446. [PMC free article] [PubMed]
  • Hinnebusch AG. Translational regulation of yeast GCN4. A window on factors that control initiator-trna binding to the ribosome. J Biol Chem. 1997 Aug 29;272(35):21661–21664. [PubMed]
  • Hirata D, Yano K, Miyakawa T. Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the Jun family of transcriptional activators in Saccharomyces cerevisiae. Mol Gen Genet. 1994 Feb;242(3):250–256. [PubMed]
  • Jacobson A, Peltz SW. Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem. 1996;65:693–739. [PubMed]
  • Kozak M. Influences of mRNA secondary structure on initiation by eukaryotic ribosomes. Proc Natl Acad Sci U S A. 1986 May;83(9):2850–2854. [PMC free article] [PubMed]
  • Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. [PMC free article] [PubMed]
  • Lesuisse E, Labbe P. Effects of cadmium and of YAP1 and CAD1/YAP2 genes on iron metabolism in the yeast Saccharomyces cerevisiae. Microbiology. 1995 Nov;141(Pt 11):2937–2943. [PubMed]
  • Linz B, Koloteva N, Vasilescu S, McCarthy JE. Disruption of ribosomal scanning on the 5'-untranslated region, and not restriction of translational initiation per se, modulates the stability of nonaberrant mRNAs in the yeast Saccharomyces cerevisiae. J Biol Chem. 1997 Apr 4;272(14):9131–9140. [PubMed]
  • Luo Z, Sachs MS. Role of an upstream open reading frame in mediating arginine-specific translational control in Neurospora crassa. J Bacteriol. 1996 Apr;178(8):2172–2177. [PMC free article] [PubMed]
  • McCarthy JE. Posttranscriptional control of gene expression in yeast. Microbiol Mol Biol Rev. 1998 Dec;62(4):1492–1553. [PMC free article] [PubMed]
  • Moye-Rowley WS, Harshman KD, Parker CS. Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins. Genes Dev. 1989 Mar;3(3):283–292. [PubMed]
  • Mueller PP, Hinnebusch AG. Multiple upstream AUG codons mediate translational control of GCN4. Cell. 1986 Apr 25;45(2):201–207. [PubMed]
  • Oliveira CC, McCarthy JE. The relationship between eukaryotic translation and mRNA stability. A short upstream open reading frame strongly inhibits translational initiation and greatly accelerates mRNA degradation in the yeast Saccharomyces cerevisiae. J Biol Chem. 1995 Apr 14;270(15):8936–8943. [PubMed]
  • Oliveira CC, Goossen B, Zanchin NI, McCarthy JE, Hentze MW, Stripecke R. Translational repression by the human iron-regulatory factor (IRF) in Saccharomyces cerevisiae. Nucleic Acids Res. 1993 Nov 25;21(23):5316–5322. [PMC free article] [PubMed]
  • Oliveira CC, van den Heuvel JJ, McCarthy JE. Inhibition of translational initiation in Saccharomyces cerevisiae by secondary structure: the roles of the stability and position of stem-loops in the mRNA leader. Mol Microbiol. 1993 Aug;9(3):521–532. [PubMed]
  • Peltz SW, Brown AH, Jacobson A. mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor. Genes Dev. 1993 Sep;7(9):1737–1754. [PubMed]
  • Ruiz-Echevarria MJ, Peltz SW. Utilizing the GCN4 leader region to investigate the role of the sequence determinants in nonsense-mediated mRNA decay. EMBO J. 1996 Jun 3;15(11):2810–2819. [PMC free article] [PubMed]
  • Ruiz-Echevarria MJ, Czaplinski K, Peltz SW. Making sense of nonsense in yeast. Trends Biochem Sci. 1996 Nov;21(11):433–438. [PubMed]
  • Ruiz-Echevarría MJ, González CI, Peltz SW. Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA. EMBO J. 1998 Jan 15;17(2):575–589. [PMC free article] [PubMed]
  • Ruiz-Echevarría MJ, Yasenchak JM, Han X, Dinman JD, Peltz SW. The upf3 protein is a component of the surveillance complex that monitors both translation and mRNA turnover and affects viral propagation. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8721–8726. [PMC free article] [PubMed]
  • Schiestl RH, Gietz RD. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet. 1989 Dec;16(5-6):339–346. [PubMed]
  • Schnell N, Entian KD. Identification and characterization of a Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron chelators. Eur J Biochem. 1991 Sep 1;200(2):487–493. [PubMed]
  • Thireos G, Penn MD, Greer H. 5' untranslated sequences are required for the translational control of a yeast regulatory gene. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5096–5100. [PMC free article] [PubMed]
  • Turton HE, Dawes IW, Grant CM. Saccharomyces cerevisiae exhibits a yAP-1-mediated adaptive response to malondialdehyde. J Bacteriol. 1997 Feb;179(4):1096–1101. [PMC free article] [PubMed]
  • Vega Laso MR, Zhu D, Sagliocco F, Brown AJ, Tuite MF, McCarthy JE. Inhibition of translational initiation in the yeast Saccharomyces cerevisiae as a function of the stability and position of hairpin structures in the mRNA leader. J Biol Chem. 1993 Mar 25;268(9):6453–6462. [PubMed]
  • Vilela C, Linz B, Rodrigues-Pousada C, McCarthy JE. The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 1998 Mar 1;26(5):1150–1159. [PMC free article] [PubMed]
  • Werner M, Feller A, Messenguy F, Piérard A. The leader peptide of yeast gene CPA1 is essential for the translational repression of its expression. Cell. 1987 Jun 19;49(6):805–813. [PubMed]
  • Wu A, Wemmie JA, Edgington NP, Goebl M, Guevara JL, Moye-Rowley WS. Yeast bZip proteins mediate pleiotropic drug and metal resistance. J Biol Chem. 1993 Sep 5;268(25):18850–18858. [PubMed]
  • Yun DF, Laz TM, Clements JM, 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. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...