Regulated translational bypass of stop codons in yeast.

Stop codons are used to signal the ribosome to terminate the decoding of an mRNA template. Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough. These include both genetic and epigenetic mechanisms. Rather than being a translation 'error', stop-codon readthrough can have important effects on other cellular processes such as mRNA degradation and, in some cases, can confer a beneficial phenotype to the cell.

[1]  G. Varani,et al.  Eukaryotic translation initiation: there are (at least) two sides to every story , 2000, Nature Structural Biology.

[2]  Ian A. Williams,et al.  Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae. , 2004, Nucleic acids research.

[3]  C. Samakovlis,et al.  Translational readthrough in the hdc mRNA generates a novel branching inhibitor in the drosophila trachea. , 1998, Genes & development.

[4]  P. Farabaugh,et al.  Translational Accuracy during Exponential, Postdiauxic, and Stationary Growth Phases in Saccharomyces cerevisiae , 2004, Eukaryotic Cell.

[5]  S. Champ,et al.  The Glutamine Residue of the Conserved GGQ Motif in Saccharomyces cerevisiae Release Factor eRF1 Is Methylated by the Product of the YDR140w Gene* , 2005, Journal of Biological Chemistry.

[6]  S. Inge-Vechtomov,et al.  Recessive mutations in SUP35 and SUP45 genes coding for translation release factors affect chromosome stability in Saccharomyces cerevisiae , 2000, Current Genetics.

[7]  S. Liebman,et al.  Allosuppressors that enhance the efficiency of omnipotent suppressors in Saccharomyces cerevisiae. , 1987, Genetics.

[8]  G. Wagner,et al.  The mRNA cap-binding protein eIF4E in post-transcriptional gene expression , 2004, Nature Structural &Molecular Biology.

[9]  D. Botstein,et al.  Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. , 2001, Molecular biology of the cell.

[10]  S. Peltz,et al.  Mtt1 is a Upf1-like helicase that interacts with the translation termination factors and whose overexpression can modulate termination efficiency. , 2000, RNA.

[11]  Måns Ehrenberg,et al.  Splitting of the posttermination ribosome into subunits by the concerted action of RRF and EF-G. , 2005, Molecular cell.

[12]  S. Hoshino,et al.  The GTP-binding Release Factor eRF3 as a Key Mediator Coupling Translation Termination to mRNA Decay* , 2004, Journal of Biological Chemistry.

[13]  D. Bedwell,et al.  GTP Hydrolysis by eRF3 Facilitates Stop Codon Decoding during Eukaryotic Translation Termination , 2004, Molecular and Cellular Biology.

[14]  Isabelle Hatin,et al.  Impact of the six nucleotides downstream of the stop codon on translation termination , 2001, EMBO reports.

[15]  M. Rakwalska,et al.  Polypeptide chain termination and stop codon readthrough on eukaryotic ribosomes , 2005, Reviews of physiology, biochemistry and pharmacology.

[16]  M. Tuite,et al.  The [PSI+] prion of yeast: a problem of inheritance. , 2006, Methods.

[17]  Haiwei Song,et al.  The enzymes and control of eukaryotic mRNA turnover , 2004, Nature Structural &Molecular Biology.

[18]  Lev L. Kisselev,et al.  In Vitro Reconstitution of Eukaryotic Translation Reveals Cooperativity between Release Factors eRF1 and eRF3 , 2006, Cell.

[19]  D. Bedwell,et al.  Tpa1p Is Part of an mRNP Complex That Influences Translation Termination, mRNA Deadenylation, and mRNA Turnover in Saccharomyces cerevisiae , 2006, Molecular and Cellular Biology.

[20]  M. Ruiz-Echevarría,et al.  The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs. , 1998, Genes & development.

[21]  L. Kisselev,et al.  Termination of translation in eukaryotes. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[22]  M. Samsonova,et al.  Reversions to respiratory competence of omnipotent sup45 suppressor mutants may be caused by secondary sup45 mutations , 1995, Current Genetics.

[23]  M. DePristo,et al.  Missense meanderings in sequence space: a biophysical view of protein evolution , 2005, Nature Reviews Genetics.

[24]  S. Mottagui-Tabar,et al.  The second to last amino acid in the nascent peptide as a codon context determinant. , 1994, The EMBO journal.

[25]  R. Losson,et al.  Interference of nonsense mutations with eukaryotic messenger RNA stability. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Marina V. Rodnina,et al.  Kinetic Analysis of Interaction of Eukaryotic Release Factor 3 with Guanine Nucleotides* , 2006, Journal of Biological Chemistry.

[27]  Mark Gerstein,et al.  A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution. , 2002, Journal of molecular biology.

[28]  A. Podtelejnikov,et al.  Yeast poly(A)-binding protein Pab1 shuttles between the nucleus and the cytoplasm and functions in mRNA export. , 2005, RNA.

[29]  D. Bedwell,et al.  Eukaryotic Release Factor 1 Phosphorylation by CK2 Protein Kinase Is Dynamic but Has Little Effect on the Efficiency of Translation Termination in Saccharomyces cerevisiae , 2006, Eukaryotic Cell.

[30]  M. Rakwalska,et al.  The Ribosome-Bound Chaperones RAC and Ssb1/2p Are Required for Accurate Translation in Saccharomyces cerevisiae , 2004, Molecular and Cellular Biology.

[31]  T. Merkulova,et al.  Translation termination in eukaryotes: polypeptide release factor eRF1 is composed of functionally and structurally distinct domains. , 2000, RNA.

[32]  L. Frolova,et al.  Stop codons and UGG promote efficient binding of the polypeptide release factor eRF1 to the ribosomal A site. , 2003, Journal of molecular biology.

[33]  M. Tuite,et al.  Translation termination efficiency can be regulated in Saccharomyces cerevisiae by environmental stress through a prion‐mediated mechanism , 1999, The EMBO journal.

[34]  R. Parker,et al.  Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation , 2006, Nature.

[35]  Mike Tyers,et al.  BioGRID: a general repository for interaction datasets , 2005, Nucleic Acids Res..

[36]  M. Ehrenberg,et al.  Class-1 release factor eRF1 promotes GTP binding by class-2 release factor eRF3. , 2006, Biochimie.

[37]  F. Sherman,et al.  The Yeast Translation Release Factors Mrf1p and Sup45p (eRF1) Are Methylated, Respectively, by the Methyltransferases Mtq1p and Mtq2p* , 2006, Journal of Biological Chemistry.

[38]  M. Clemens,et al.  Initiation factor modifications in the preapoptotic phase , 2005, Cell Death and Differentiation.

[39]  Susan Lindquist,et al.  Prions as adaptive conduits of memory and inheritance , 2005, Nature Reviews Genetics.

[40]  L. Kisselev,et al.  Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. , 1995, The EMBO journal.

[41]  M. Philippe,et al.  Poly(A)-Binding Protein Acts in Translation Termination via Eukaryotic Release Factor 3 Interaction and Does Not Influence [PSI+] Propagation , 2002, Molecular and Cellular Biology.

[42]  C. Pal Yeast prions and evolvability. , 2001, Trends in genetics : TIG.

[43]  A. R. Merrill,et al.  The life and death of translation elongation factor 2. , 2006, Biochemical Society transactions.

[44]  R. Wickner,et al.  Yeast prions [URE3] and [PSI+] are diseases. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Shobha Vasudevan,et al.  Non-stop decay--a new mRNA surveillance pathway. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[46]  C. Samakovlis,et al.  A novel stop codon readthrough mechanism produces functional Headcase protein in Drosophila trachea , 2001, EMBO reports.

[47]  S. Hoshino,et al.  The Eukaryotic Polypeptide Chain Releasing Factor (eRF3/GSPT) Carrying the Translation Termination Signal to the 3′-Poly(A) Tail of mRNA , 1999, The Journal of Biological Chemistry.

[48]  L. Partridge,et al.  Natural Selection: Evolving evolvability , 2000, Nature.

[49]  E. O’Shea,et al.  Global analysis of protein expression in yeast , 2003, Nature.

[50]  D. Bedwell,et al.  The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae. , 1995, Journal of molecular biology.

[51]  M. Ter‐Avanesyan,et al.  Transcriptional Regulation of SUP35 and SUP45 in Saccharomyces cerevisiae , 1997 .

[52]  D. Bedwell,et al.  Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae. , 2004, RNA.

[53]  L. Valente,et al.  Yeast as a sensor of factors affecting the accuracy of protein synthesis , 2003, Cellular and Molecular Life Sciences CMLS.

[54]  A. Makarov,et al.  Termination of translation in eukaryotes is mediated by the quaternary eRF1•eRF3•GTP•Mg2+ complex. The biological roles of eRF3 and prokaryotic RF3 are profoundly distinct , 2006, Nucleic acids research.

[55]  A. Benko,et al.  Competition between a sterol biosynthetic enzyme and tRNA modification in addition to changes in the protein synthesis machinery causes altered nonsense suppression. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[56]  A. Haenni,et al.  Codon context effect in virus translational readthrough A study in vitro of the determinants of TMV and Mo‐MuLV amber suppression , 1992, FEBS letters.

[57]  Matthew S. Sachs,et al.  Early nonsense: mRNA decay solves a translational problem , 2006, Nature Reviews Molecular Cell Biology.

[58]  F. He,et al.  Nonsense-Containing mRNAs That Accumulate in the Absence of a Functional Nonsense-Mediated mRNA Decay Pathway Are Destabilized Rapidly upon Its Restitution , 2003, Molecular and Cellular Biology.

[59]  V. Smirnov,et al.  Translation termination factors function outside of translation: yeast eRF1 interacts with myosin light chain, Mlc1p, to effect cytokinesis , 2004, Molecular microbiology.

[60]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[61]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[62]  D. Bedwell,et al.  Discrimination between defects in elongation fidelity and termination efficiency provides mechanistic insights into translational readthrough. , 2005, Journal of molecular biology.

[63]  Haiwei Song,et al.  Crystal structure and functional analysis of the eukaryotic class II release factor eRF3 from S. pombe. , 2004, Molecular cell.

[64]  A. Mankin,et al.  The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. , 2003, Molecular cell.

[65]  M. Ter‐Avanesyan,et al.  Yeast polypeptide chain release factors eRF1 and eRF3 are involved in cytoskeleton organization and cell cycle regulation. , 2002, Cell motility and the cytoskeleton.

[66]  B. Cox A recessive lethal super-suppressor mutation in yeast and other ψ phenomena , 1971, Heredity.

[67]  R. Parker,et al.  Genetic interactions between [PSI+] and nonstop mRNA decay affect phenotypic variation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Heather L. True,et al.  Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits , 2004, Nature.

[69]  T. Ideker,et al.  Integrating phenotypic and expression profiles to map arsenic-response networks , 2004, Genome Biology.

[70]  Nikolaj Blom,et al.  BIOINFORMATICS APPLICATIONS NOTE Sequence analysis NetAcet: prediction of N-terminal acetylation sites , 2004 .

[71]  O. Namy,et al.  Translational readthrough of the PDE2 stop codon modulates cAMP levels in Saccharomyces cerevisiae , 2002, Molecular microbiology.

[72]  Michel Termier,et al.  Identification of stop codon readthrough genes in Saccharomyces cerevisiae. , 2003, Nucleic acids research.

[73]  I. Stansfield,et al.  The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. , 1995, The EMBO journal.

[74]  H. True,et al.  A yeast prion provides a mechanism for genetic variation and phenotypic diversity , 2000, Nature.

[75]  S. Paushkin,et al.  Itt1p, a novel protein inhibiting translation termination in Saccharomyces cerevisiae , 2001, BMC Molecular Biology.

[76]  A. Haenni,et al.  A highly conserved eukaryotic protein family possessing properties of polypeptide chain release factor , 1994, Nature.

[77]  D. Barford,et al.  The Crystal Structure of Human Eukaryotic Release Factor eRF1—Mechanism of Stop Codon Recognition and Peptidyl-tRNA Hydrolysis , 2000, Cell.

[78]  M. Tuite,et al.  In vitro nonsense suppression in [psi+] and [psi-] cell-free lysates of Saccharomyces cerevisiae. , 1983, Proceedings of the National Academy of Sciences of the United States of America.