Specialization from synthesis: How ribosome diversity can customize protein function

It was thought that the proteins produced by ribosomes were dictated only by the sequences of the mRNAs they translated, however it is becoming apparent that subpopulations of ribosomes can have unique properties that influence the functions of the proteins they produce. Ribosomes have been engineered to discriminate between different mRNA templates or with unique decoding properties, and many new applications of unnatural ribosomes can be foreseen. In natural systems ribosomes with alternate protein and RNA composition have been shown to selectively translate specific mRNAs. As more is learned about ribosome structure and the mechanisms of translation, new opportunities to engineer ribosomes for applications in biotechnology and synthetic biology can be developed and new examples of ribosome‐mediated regulation of translation are likely to emerge in nature.

[1]  V. Ramakrishnan,et al.  How mutations in tRNA distant from the anticodon affect the fidelity of decoding , 2010, Nature Structural &Molecular Biology.

[2]  Peter G Schultz,et al.  An Expanded Eukaryotic Genetic Code , 2003, Science.

[3]  Shifeng Xue,et al.  Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning , 2011, Cell.

[4]  R. Agrawal,et al.  Structural aspects of mitochondrial translational apparatus. , 2012, Current opinion in structural biology.

[5]  The structure of the 80S ribosome from Trypanosoma cruzi reveals unique rRNA components. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  L. Chavatte,et al.  Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes , 2005, Nature Structural &Molecular Biology.

[7]  J. Chin,et al.  Functional epitopes at the ribosome subunit interface , 2006, Nature chemical biology.

[8]  E. Enerly,et al.  Silencing the Drosophila ribosomal protein L14 gene using targeted RNA interference causes distinct somatic anomalies. , 2003, Gene.

[9]  F. Rodríguez-Valera,et al.  Intragenomic 16S rDNA Divergence in Haloarcula marismortui Is an Adaptation to Different Temperatures , 2007, Journal of Molecular Evolution.

[10]  Peter G Schultz,et al.  An expanded genetic code with a functional quadruplet codon. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Böck,et al.  Selenocysteine tRNA‐specific elongation factor SelB is a structural chimaera of elongation and initiation factors , 2005, The EMBO journal.

[12]  N. Ban,et al.  Atomic structures of the eukaryotic ribosome. , 2012, Trends in biochemical sciences.

[13]  M. Huynen,et al.  C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation , 2012, Nucleic acids research.

[14]  Bernd Bukau,et al.  The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins , 2009, Nature Structural &Molecular Biology.

[15]  I. Moll,et al.  An unexpected type of ribosomes induced by kasugamycin: a look into ancestral times of protein synthesis? , 2009, Molecular cell.

[16]  S. Carr,et al.  A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology , 2008, Cell.

[17]  T. Glaser,et al.  Ribosomal protein L24 defect in Belly spot and tail (Bst), a mouse Minute , 2004, Development.

[18]  M. Ibba,et al.  Aminoacyl-tRNA synthesis and translational quality control. , 2009, Annual review of microbiology.

[19]  Pohl Milón,et al.  Kinetic control of translation initiation in bacteria , 2012, Critical reviews in biochemistry and molecular biology.

[20]  H. Wittmann,et al.  Biological Sciences: Ribosomal Proteins: Variation of the Protein Composition in Escherichia coli Ribosomes as Function of Growth Rate , 1972, Nature.

[21]  E. Salmon,et al.  Localization and anchoring of mRNA in budding yeast , 1999, Current Biology.

[22]  J. Sengupta,et al.  Structural Diversity in Bacterial Ribosomes: Mycobacterial 70S Ribosome Structure Reveals Novel Features , 2012, PloS one.

[23]  Jason R. Swedlow,et al.  Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast , 1997, Nature.

[24]  J. Donovan,et al.  Threading the needle: getting selenocysteine into proteins. , 2010, Antioxidants & redox signaling.

[25]  Satoru Kobayashi,et al.  Presence of mitochondria-type ribosomes outside mitochondria in germ plasm of Drosophila embryos , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Jon R Lorsch,et al.  A mechanistic overview of translation initiation in eukaryotes , 2012, Nature Structural &Molecular Biology.

[27]  W. Gilbert,et al.  Functional specialization of ribosomes? , 2011, Trends in biochemical sciences.

[28]  Shifeng Xue,et al.  Specialized ribosomes: a new frontier in gene regulation and organismal biology , 2012, Nature Reviews Molecular Cell Biology.

[29]  W. Leinfelder,et al.  Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine , 1988, Nature.

[30]  S. Whelan,et al.  A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs , 2012, Proceedings of the National Academy of Sciences.

[31]  J. Chin,et al.  Evolved orthogonal ribosomes enhance the efficiency of synthetic genetic code expansion , 2007, Nature Biotechnology.

[32]  S W Liebman,et al.  Chimeric rRNAs containing the GTPase centers of the developmentally regulated ribosomal rRNAs of Plasmodium falciparum are functionally distinct. , 1998, RNA.

[33]  J. Whelan,et al.  MRPS27 is a pentatricopeptide repeat domain protein required for the translation of mitochondrially encoded proteins , 2012, FEBS letters.

[34]  Pamela A. Silver,et al.  Functional Specificity among Ribosomal Proteins Regulates Gene Expression , 2007, Cell.

[35]  H. Engelberg-Kulka,et al.  Escherichia coli MazF Leads to the Simultaneous Selective Synthesis of Both “Death Proteins” and “Survival Proteins” , 2009, PLoS genetics.

[36]  N. Nakashima,et al.  Eukaryotic ribosomal protein RPS25 interacts with the conserved loop region in a dicistroviral intergenic internal ribosome entry site , 2007, Nucleic acids research.

[37]  N. Ban,et al.  Structural insights into eukaryotic ribosomes and the initiation of translation. , 2012, Current opinion in structural biology.

[38]  M. Byrne A role for the ribosome in development. , 2009, Trends in plant science.

[39]  Dieter Söll,et al.  Natural expansion of the genetic code. , 2007, Nature chemical biology.

[40]  F. Briani,et al.  S1 ribosomal protein and the interplay between translation and mRNA decay , 2011, Nucleic acids research.

[41]  P. Klimov,et al.  Repeated parallel evolution of minimal rRNAs revealed from detailed comparative analysis. , 2011, The Journal of heredity.

[42]  Junjie Zhang,et al.  Characterization of the Interactions within the mazEF Addiction Module of Escherichia coli* , 2003, Journal of Biological Chemistry.

[43]  Wayne A. Decatur,et al.  rRNA modifications and ribosome function. , 2002, Trends in biochemical sciences.

[44]  N. Brot,et al.  The enzymatic acetylation of E. coli ribosomal protein L 12 . , 1972, Biochemical and biophysical research communications.

[45]  S Ramagopal,et al.  Induction of cell-specific ribosomal proteins in aggregation-competent nonmorphogenetic Dictyostelium discoideum. , 1990, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[46]  Kim Nasmyth,et al.  ASH1 mRNA localization in yeast involves multiple secondary structural elementsand Ash1 protein translation , 1999, Current Biology.

[47]  G. Edelman,et al.  The Ribosome Filter Redux , 2007, Cell cycle.

[48]  G. Edelman,et al.  Isolation and identification of short nucleotide sequences that affect translation initiation in Saccharomyces cerevisiae , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Michael Ashburner,et al.  The ribosomal protein genes and Minute loci of Drosophila melanogaster , 2007, Genome Biology.

[50]  A. Böck,et al.  The many levels of control on bacterial selenoprotein synthesis. , 2009, Biochimica et biophysica acta.

[51]  J. Chin,et al.  Cellular logic with orthogonal ribosomes. , 2005, Journal of the American Chemical Society.

[52]  D. Weijers,et al.  An Arabidopsis Minute-like phenotype caused by a semi-dominant mutation in a RIBOSOMAL PROTEIN S5 gene. , 2001, Development.

[53]  C. Vonrhein,et al.  Structure of the 30S ribosomal subunit , 2000, Nature.

[54]  J. Chin,et al.  Synthesizing cellular networks from evolved ribosome-mRNA pairs. , 2006, Biochemical Society transactions.

[55]  R. Gourse,et al.  rRNA transcription in Escherichia coli. , 2004, Annual review of genetics.

[56]  Klaus Schulten,et al.  The role of L1 stalk-tRNA interaction in the ribosome elongation cycle. , 2010, Journal of molecular biology.

[57]  R. Agrawal,et al.  Structure of a mitochondrial ribosome with minimal RNA , 2009, Proceedings of the National Academy of Sciences.

[58]  I. Moll,et al.  Selective translation during stress in Escherichia coli. , 2012, Trends in biochemical sciences.

[59]  P G Schultz,et al.  Expanding the Genetic Code of Escherichia coli , 2001, Science.

[60]  J. Chin,et al.  Expanding the Genetic Code of an Animal , 2011, Journal of the American Chemical Society.

[61]  S. Kobayashi,et al.  Presence of mitochondrial large ribosomal RNA outside mitochondria in germ plasm of Drosophila melanogaster. , 1993, Science.

[62]  N. Ban,et al.  Crystal Structure of the Eukaryotic 40S Ribosomal Subunit in Complex with Initiation Factor 1 , 2011, Science.

[63]  P. Cunningham,et al.  Genetic analysis of the Shine-Dalgarno interaction: selection of alternative functional mRNA-rRNA combinations. , 1996, RNA.

[64]  Peter Gustavsson,et al.  The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia , 1999, Nature Genetics.

[65]  M. Farach-Carson,et al.  Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[66]  Dieter Söll,et al.  From one amino acid to another: tRNA-dependent amino acid biosynthesis , 2008, Nucleic acids research.

[67]  O. Uhlenbeck,et al.  Specificity of the ribosomal A site for aminoacyl-tRNAs , 2008, Nucleic acids research.

[68]  G. Hart,et al.  O-GlcNAc Cycling Enzymes Associate with the Translational Machinery and Modify Core Ribosomal Proteins , 2010, Molecular biology of the cell.

[69]  Steven J. Marygold,et al.  Drosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone , 2011, PLoS genetics.

[70]  V. Gladyshev,et al.  Dual functions of codons in the genetic code , 2010, Critical reviews in biochemistry and molecular biology.

[71]  J. Kutok,et al.  Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. , 2011, Blood.

[72]  Gene-Wei Li,et al.  The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria , 2012, Nature.

[73]  T. Earnest,et al.  Crystal Structure of the Ribosome at 5.5 Å Resolution , 2001, Science.

[74]  Sergey V. Melnikov,et al.  The structure of the eukaryotic ribosome at 3.0 angstrom resolution. , 2011 .

[75]  J. Chin,et al.  Expanding the genetic code of Drosophila melanogaster. , 2012, Nature chemical biology.

[76]  S. Thompson,et al.  RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs. , 2009, Genes & development.

[77]  R. Agrawal,et al.  Structure of the Mammalian Mitochondrial Ribosome Reveals an Expanded Functional Role for Its Component Proteins , 2003, Cell.

[78]  A. Schambach,et al.  Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia. , 2011, Blood.

[79]  I. Brierley,et al.  Non-canonical translation in RNA viruses , 2012, The Journal of general virology.

[80]  J. Abkowitz,et al.  Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis. , 2012, Experimental hematology.

[81]  August Böck,et al.  Identification of a novel translation factor necessary for the incorporation of selenocysteine into protein , 1989, Nature.

[82]  M. Yusupov,et al.  One core, two shells: bacterial and eukaryotic ribosomes , 2012, Nature Structural &Molecular Biology.

[83]  Steven J. Marygold,et al.  Genetic Analysis of RpL38 and RpL5, Two Minute Genes Located in the Centric Heterochromatin of Chromosome 2 of Drosophila melanogaster , 2005, Genetics.

[84]  G. Edelman,et al.  Differential utilization of upstream AUGs in the beta-secretase mRNA suggests that a shunting mechanism regulates translation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[85]  Peter G Schultz,et al.  Adding new chemistries to the genetic code. , 2010, Annual review of biochemistry.

[86]  N. Ban,et al.  Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6 , 2011, Science.

[87]  T. Mercer,et al.  The human mitochondrial transcriptome and the RNA‐binding proteins that regulate its expression , 2012, Wiley interdisciplinary reviews. RNA.

[88]  G. Edelman,et al.  The ribosome filter hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[89]  M. Yusupov,et al.  Crystal structure of the 80S yeast ribosome. , 2012, Current opinion in structural biology.

[90]  T. Wood,et al.  Construction of a specialized‐ribosome vector or cloned‐gene expression in E. coli , 1991, Biotechnology and bioengineering.

[91]  T. Burke,et al.  An engineered selenocysteine defines a unique class of antibody derivatives , 2008, Proceedings of the National Academy of Sciences.

[92]  Role of mitochondrial ribosome-dependent translation in germline formation in Drosophila embryos , 2005, Mechanisms of Development.

[93]  R. Horos,et al.  Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. , 2012, Blood.

[94]  R. Lehmann,et al.  Germ Versus Soma Decisions: Lessons from Flies and Worms , 2007, Science.

[95]  Wei Xu,et al.  Impaired Control of IRES-Mediated Translation in X-Linked Dyskeratosis Congenita , 2006, Science.

[96]  L. Flohé The labour pains of biochemical selenology: the history of selenoprotein biosynthesis. , 2009, Biochimica et biophysica acta.

[97]  T. McCutchan,et al.  Structurally distinct, stage-specific ribosomes occur in Plasmodium. , 1987, Science.

[98]  N. Malys,et al.  Translation initiation: variations in the mechanism can be anticipated , 2011, Cellular and Molecular Life Sciences.

[99]  António Amorim,et al.  The human RPS4 paralogue on Yq11.223 encodes a structurally conserved ribosomal protein and is preferentially expressed during spermatogenesis , 2010, BMC Molecular Biology.

[100]  Wei Zhang,et al.  GTPase activation of elongation factor EF‐Tu by the ribosome during decoding , 2009, The EMBO journal.

[101]  M. Berry,et al.  Regulation and function of selenoproteins in human disease. , 2009, The Biochemical journal.

[102]  C. Robinson,et al.  Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. , 2012, Nature chemical biology.

[103]  Isabella Moll,et al.  Selective Translation of Leaderless mRNAs by Specialized Ribosomes Generated by MazF in Escherichia coli , 2011, Cell.

[104]  Hans J C T Wessels,et al.  A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome , 2010, The EMBO journal.

[105]  M. Whitt,et al.  The minimal conserved transcription stop-start signal promotes stable expression of a foreign gene in vesicular stomatitis virus , 1996, Journal of virology.

[106]  P. Schultz,et al.  Genetic incorporation of unnatural amino acids into proteins in mammalian cells , 2007, Nature Methods.

[107]  A. Böck,et al.  Escherichia coli genes whose products are involved in selenium metabolism , 1988, Journal of bacteriology.

[108]  Jason W. Chin,et al.  Designer proteins: applications of genetic code expansion in cell biology , 2012, Nature Reviews Molecular Cell Biology.

[109]  G. Dittmar,et al.  Cell Cycle–Regulated Modification of the Ribosome by a Variant Multiubiquitin Chain , 2000, Cell.

[110]  A. Serganov,et al.  Structured mRNAs Regulate Translation Initiation by Binding to the Platform of the Ribosome , 2007, Cell.

[111]  L. Spremulli,et al.  Mechanism of protein biosynthesis in mammalian mitochondria. , 2012, Biochimica et biophysica acta.

[112]  A. Hüttenhofer,et al.  Selenocysteine inserting RNA elements modulate GTP hydrolysis of elongation factor SelB. , 1998, Biochemistry.

[113]  B. Birren,et al.  Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae , 2004, Nature.

[114]  V. Ramakrishnan,et al.  What recent ribosome structures have revealed about the mechanism of translation , 2009, Nature.

[115]  Isabella Moll,et al.  Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs. , 2004, Nucleic acids research.

[116]  A. Amsterdam,et al.  Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish , 2009, Developmental dynamics : an official publication of the American Association of Anatomists.

[117]  G. King,et al.  Direct visualization of disulfide bonds through diselenide proxies using 77Se NMR spectroscopy. , 2009, Angewandte Chemie.

[118]  J. Whelan,et al.  Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation , 2009, FEBS letters.

[119]  Jennifer A. Doudna,et al.  The Crystal Structure of the Signal Recognition Particle in Complex with Its Receptor , 2011, Science.

[120]  J. Chin,et al.  Synthesis of orthogonal transcription-translation networks , 2009, Proceedings of the National Academy of Sciences.

[121]  Jason W. Chin,et al.  Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome , 2010, Nature.

[122]  H. Noller,et al.  Reconstitution of functional 50S ribosomes from in vitro transcripts of Bacillus stearothermophilus 23S rRNA. , 1999, Biochemistry.

[123]  B. S. Laursen,et al.  Initiation of Protein Synthesis in Bacteria , 2005, Microbiology and Molecular Biology Reviews.

[124]  D. Bodine,et al.  A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia. , 2010, Blood.

[125]  W. Paik,et al.  Methylation of Ribosomal Proteins in Escherichia coli , 1974, Journal of bacteriology.

[126]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[127]  D. Söll,et al.  Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems , 2010, FEBS letters.

[128]  Martijn A. Huynen,et al.  Reconstructing the evolution of the mitochondrial ribosomal proteome , 2007, Nucleic acids research.

[129]  Koichi Ito,et al.  tRNA mimicry in translation termination and beyond , 2011, Wiley interdisciplinary reviews. RNA.

[130]  R. Horos,et al.  Molecular mechanisms of pathology and treatment in Diamond Blackfan Anaemia , 2012, British journal of haematology.

[131]  K. Caban,et al.  Selenocysteine Insertion Sequence (SECIS)-binding Protein 2 Alters Conformational Dynamics of Residues Involved in tRNA Accommodation in 80 S Ribosomes* , 2012, The Journal of Biological Chemistry.

[132]  O. Rackham,et al.  Engineered rRNA enhances the efficiency of selenocysteine incorporation during translation. , 2013, Journal of the American Chemical Society.

[133]  A. Rich,et al.  Ribosome-catalyzed ester formation. , 1970, Biochemistry.

[134]  Aleksandra Filipovska,et al.  Building a Parallel Metabolism within the Cell. , 2008, ACS chemical biology.

[135]  Sergey Melnikov,et al.  The Structure of the Eukaryotic Ribosome at 3.0 Å Resolution , 2011, Science.

[136]  T. Blumenthal,et al.  Trans‐splicing , 2011, Wiley interdisciplinary reviews. RNA.

[137]  H. D. de Boer,et al.  Specialized ribosome system: preferential translation of a single mRNA species by a subpopulation of mutated ribosomes in Escherichia coli. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[138]  Elias S. J. Arnér,et al.  Selenocysteine in proteins-properties and biotechnological use. , 2005, Biochimica et biophysica acta.

[139]  Farren J. Isaacs,et al.  RNA synthetic biology , 2006, Nature Biotechnology.

[140]  K. Nasmyth,et al.  Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. , 1997, Science.

[141]  H. Jakubowski Quality control in tRNA charging , 2012, Wiley interdisciplinary reviews. RNA.

[142]  J. Hofsteenge,et al.  Identification of the 40 S ribosomal protein S6 phosphorylation sites induced by cycloheximide. , 1988, The Journal of biological chemistry.

[143]  J. Chin,et al.  A network of orthogonal ribosome·mRNA pairs , 2005, Nature chemical biology.

[144]  Ira Herskowitz,et al.  The Khd1 protein, which has three KH RNA‐binding motifs, is required for proper localization of ASH1 mRNA in yeast , 2002, The EMBO journal.