Measurements of translation initiation from all 64 codons in E. coli

Our understanding of translation is one cornerstone of molecular biology that underpins our capacity to engineer living matter. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are typically considered as the “start codons” for translation initiation in Escherichia coli (E. coli). Translation is typically not thought to initiate from the 61 remaining codons. Here, we systematically quantified translation initiation in E. coli from all 64 triplet codons. We detected protein synthesis above background initiating from at least 46 codons. Translation initiated from these non-canonical start codons at levels ranging from 0.01% to 2% relative to AUG. Translation initiation from non-canonical start codons may contribute to the synthesis of peptides in both natural and synthetic biological systems

[1]  Suzanne M. Paley,et al.  The MetaCyc database of metabolic pathways and enzymes , 2017, Nucleic Acids Res..

[2]  Michael H. Schwartz,et al.  Global tRNA misacylation induced by anaerobiosis and antibiotic exposure broadly increases stress resistance in Escherichia coli , 2016, Nucleic acids research.

[3]  Natalia N. Ivanova,et al.  Facile Recoding of Selenocysteine in Nature. , 2016, Angewandte Chemie.

[4]  Christopher A. Voigt,et al.  Genetic circuit design automation , 2016, Science.

[5]  R. Aebersold,et al.  The quantitative and condition-dependent Escherichia coli proteome , 2015, Nature Biotechnology.

[6]  Christopher A. Voigt,et al.  Automated design of synthetic ribosome binding sites to control protein expression , 2016 .

[7]  Henrike Niederholtmeyer,et al.  Rapid cell-free forward engineering of novel genetic ring oscillators , 2015, eLife.

[8]  C. Gualerzi,et al.  Initiation of mRNA translation in bacteria: structural and dynamic aspects , 2015, Cellular and Molecular Life Sciences.

[9]  U. Varshney,et al.  Is the cellular initiation of translation an exclusive property of the initiator tRNAs? , 2015, RNA biology.

[10]  David J. Anderson,et al.  Ventromedial hypothalamic neurons control a defensive emotion state , 2015, eLife.

[11]  James J. Collins,et al.  Using Targeted Chromatin Regulators to Engineer Combinatorial and Spatial Transcriptional Regulation , 2014, Cell.

[12]  Axel Visel,et al.  Stop codon reassignments in the wild , 2014, Science.

[13]  G. Church,et al.  Recoding the genetic code with selenocysteine. , 2014, Angewandte Chemie.

[14]  K. Asano.  Why is start codon selection so precise in eukaryotes? , 2014, Translation.

[15]  Christopher A. Voigt,et al.  Genomic Mining of Prokaryotic Repressors for Orthogonal Logic Gates , 2013, Nature chemical biology.

[16]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[17]  Christopher A. Voigt,et al.  Advances in genetic circuit design: novel biochemistries, deep part mining, and precision gene expression. , 2013, Current opinion in chemical biology.

[18]  Sriram Kosuri,et al.  Causes and Effects of N-Terminal Codon Bias in Bacterial Genes , 2013, Science.

[19]  Peter G. Schultz,et al.  Genomically Recoded Organisms Expand Biological Functions , 2013, Science.

[20]  T. Oshima,et al.  Direct assessment of transcription fidelity by high-resolution RNA sequencing , 2013, Nucleic acids research.

[21]  Vivek K. Mutalik,et al.  Composability of regulatory sequences controlling transcription and translation in Escherichia coli , 2013, Proceedings of the National Academy of Sciences.

[22]  Christopher A. Voigt,et al.  Characterization of 582 natural and synthetic terminators and quantification of their design constraints , 2013, Nature Methods.

[23]  Vivek K. Mutalik,et al.  Measurement and modeling of intrinsic transcription terminators , 2013, Nucleic acids research.

[24]  Drew Endy,et al.  Precise and reliable gene expression via standard transcription and translation initiation elements , 2013, Nature Methods.

[25]  Rob Phillips,et al.  Tuning Promoter Strength through RNA Polymerase Binding Site Design in Escherichia coli , 2012, PLoS Comput. Biol..

[26]  K. Huse,et al.  Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting , 2012, Genome research.

[27]  Erez Lieberman Aiden,et al.  The expanding scope of DNA sequencing , 2012, Nature Biotechnology.

[28]  Christopher A. Voigt,et al.  Ribozyme-based insulator parts buffer synthetic circuits from genetic context , 2012, Nature Biotechnology.

[29]  B. Shen,et al.  Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution , 2012, Proceedings of the National Academy of Sciences.

[30]  Brock F. Binkowski,et al.  Engineered Luciferase Reporter from a Deep Sea Shrimp Utilizing a Novel Imidazopyrazinone Substrate , 2012, ACS chemical biology.

[31]  Nicholas C Tang,et al.  DNA synthesis, assembly and applications in synthetic biology. , 2012, Current opinion in chemical biology.

[32]  César A. Hidalgo,et al.  Proto-genes and de novo gene birth , 2012, Nature.

[33]  Pohl Milón,et al.  Real-time assembly landscape of bacterial 30S translation initiation complex , 2012, Nature Structural &Molecular Biology.

[34]  E. Marcotte,et al.  Insights into the regulation of protein abundance from proteomic and transcriptomic analyses , 2012, Nature Reviews Genetics.

[35]  J. Weissman,et al.  Selective Ribosome Profiling Reveals the Cotranslational Chaperone Action of Trigger Factor In Vivo , 2011, Cell.

[36]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[37]  Conrad Steenberg,et al.  NUPACK: Analysis and design of nucleic acid systems , 2011, J. Comput. Chem..

[38]  Pedro M. Valero-Mora,et al.  ggplot2: Elegant Graphics for Data Analysis , 2010 .

[39]  Paul J. Choi,et al.  Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells , 2010, Science.

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

[41]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[42]  Carola Engler,et al.  Golden Gate Shuffling: A One-Pot DNA Shuffling Method Based on Type IIs Restriction Enzymes , 2009, PloS one.

[43]  D. G. Gibson,et al.  Enzymatic assembly of DNA molecules up to several hundred kilobases , 2009, Nature Methods.

[44]  Nicholas T. Ingolia,et al.  Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling , 2009, Science.

[45]  Robert Gentleman,et al.  flowCore: a Bioconductor package for high throughput flow cytometry , 2009, BMC Bioinformatics.

[46]  Ju Han Kim,et al.  Identifying set-wise differential co-expression in gene expression microarray data , 2009, BMC Bioinformatics.

[47]  S. Marzi,et al.  A structural view of translation initiation in bacteria , 2009, Cellular and Molecular Life Sciences.

[48]  R. Simons,et al.  A single mutation in the IF3 N-terminal domain perturbs the fidelity of translation initiation at three levels. , 2008, Journal of molecular biology.

[49]  A. Villegas,et al.  An analysis of initiation codon utilization in the Domain Bacteria - concerns about the quality of bacterial genome annotation. , 2008, Microbiology.

[50]  T. Hothorn,et al.  Simultaneous Inference in General Parametric Models , 2008, Biometrical journal. Biometrische Zeitschrift.

[51]  K. Fredrick,et al.  Characterization of 16S rRNA mutations that decrease the fidelity of translation initiation. , 2007, RNA.

[52]  Paul F Agris,et al.  tRNA's wobble decoding of the genome: 40 years of modification. , 2007, Journal of molecular biology.

[53]  P. Farabaugh,et al.  The frequency of translational misreading errors in E. coli is largely determined by tRNA competition. , 2006, RNA.

[54]  Ramasubbu Sankararamakrishnan,et al.  A Survey of mRNA Sequences with a Non-AUG Start Codon in RefSeq Database , 2006, Journal of biomolecular structure & dynamics.

[55]  T. Terwilliger,et al.  Engineering and characterization of a superfolder green fluorescent protein , 2006, Nature Biotechnology.

[56]  Nathan C Shaner,et al.  A guide to choosing fluorescent proteins , 2005, Nature Methods.

[57]  G. Stephanopoulos,et al.  Tuning genetic control through promoter engineering. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Alain Xayaphoummine,et al.  Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots , 2005, Nucleic Acids Res..

[59]  Yael Garten,et al.  Extraction of transcription regulatory signals from genome-wide DNA–protein interaction data , 2005, Nucleic acids research.

[60]  R. Rosenberger,et al.  An estimate of the frequency of in vivo transcriptional errors at a nonsense codon in Escherichia coli , 2004, Molecular and General Genetics MGG.

[61]  M. Inouye,et al.  Enhancement of Translation Initiation by A/T-Rich Sequences Downstream of the Initiation Codon in Escherichia coli , 2004, Journal of Molecular Microbiology and Biotechnology.

[62]  S. Blair Hedges,et al.  The origin and evolution of model organisms , 2002, Nature Reviews Genetics.

[63]  W. Szybalski,et al.  Conditionally amplifiable BACs: switching from single-copy to high-copy vectors and genomic clones. , 2002, Genome research.

[64]  Eric Westhof,et al.  The non-Watson-Crick base pairs and their associated isostericity matrices. , 2002, Nucleic acids research.

[65]  M. Masters,et al.  Expression of the Escherichia coli pcnB gene is translationally limited using an inefficient start codon: a second chromosomal example of translation initiated at AUU , 2002, Molecular microbiology.

[66]  Takuya Ueda,et al.  Cell-free translation reconstituted with purified components , 2001, Nature Biotechnology.

[67]  U. RajBhandary,et al.  Altered discrimination of start codons and initiator tRNAs by mutant initiation factor 3. , 2001, RNA.

[68]  W. Tate,et al.  Codon bias at the 3'-side of the initiation codon is correlated with translation initiation efficiency in Escherichia coli. , 2001, Gene.

[69]  Gabriele Varani,et al.  The G·U wobble base pair , 2000 .

[70]  G. Varani,et al.  The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems. , 2000, EMBO reports.

[71]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[72]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[73]  M. Kozak.  Initiation of translation in prokaryotes and eukaryotes. , 1999, Gene.

[74]  M. Springer,et al.  Mutations that alter initiation codon discrimination by Escherichia coli initiation factor IF3. , 1999, Journal of molecular biology.

[75]  M. Springer,et al.  Discrimination by Escherichia coli initiation factor IF3 against initiation on non-canonical codons relies on complementarity rules. , 1999, Journal of molecular biology.

[76]  S. Lindquist,et al.  Hsp90 as a capacitor for morphological evolution , 1998, Nature.

[77]  S. Kain,et al.  Deletions of the Aequorea victoria Green Fluorescent Protein Define the Minimal Domain Required for Fluorescence* , 1997, The Journal of Biological Chemistry.

[78]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[79]  M. Kalapos,et al.  Polyadenylated mRNA in Escherichia coli: modulation of poly(A) RNA levels by polynucleotide phosphorylase and ribonuclease II. , 1997, Biochimie.

[80]  R. Simons,et al.  Escherichia coli translation initiation factor 3 discriminates the initiation codon in vivo , 1996, Molecular microbiology.

[81]  M. L. Sprengart,et al.  The downstream box: an efficient and independent translation initiation signal in Escherichia coli. , 1996, The EMBO journal.

[82]  M Bjerknes,et al.  Determination of the optimal aligned spacing between the Shine-Dalgarno sequence and the translation initiation codon of Escherichia coli mRNAs. , 1994, Nucleic acids research.

[83]  T. D. Schneider,et al.  Quantitative analysis of ribosome binding sites in E.coli. , 1994, Nucleic acids research.

[84]  M. Masters,et al.  The pcnB gene of Escherichia coli, which is required for ColE1 copy number maintenance, is dispensable , 1993, Journal of bacteriology.

[85]  Y. Mechulam,et al.  Importance of formylability and anticodon stem sequence to give a tRNA(Met) an initiator identity in Escherichia coli , 1993, Journal of bacteriology.

[86]  E. Goldman,et al.  Increased ribosomal accuracy increases a programmed translational frameshift in Escherichia coli. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[87]  U. RajBhandary,et al.  From elongator tRNA to initiator tRNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[88]  G. Stormo,et al.  Translation initiation in Escherichia coli: sequences within the ribosome‐binding site , 1992, Molecular microbiology.

[89]  J. Drake.  A constant rate of spontaneous mutation in DNA-based microbes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[90]  L. Gold,et al.  Domains of initiator tRNA and initiation codon crucial for initiator tRNA selection by Escherichia coli IF3. , 1990, Genes & development.

[91]  U. RajBhandary,et al.  Initiation of protein synthesis from a termination codon. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[92]  J. Parker,et al.  Errors and alternatives in reading the universal genetic code. , 1989, Microbiological reviews.

[93]  D. Peabody,et al.  Translation initiation at non-AUG triplets in mammalian cells. , 1989, The Journal of biological chemistry.

[94]  M. Dreyfus,et al.  What constitutes the signal for the initiation of protein synthesis on Escherichia coli mRNAs? , 1988, Journal of molecular biology.

[95]  P. Schimmel,et al.  Evidence for a unique first position codon-anticodon mismatch in vivo. , 1988, Journal of molecular biology.

[96]  L. Gold,et al.  Posttranscriptional regulatory mechanisms in Escherichia coli. , 1988, Annual review of biochemistry.

[97]  A. C. Looman,et al.  Influence of the codon following the AUG initiation codon on the expression of a modified lacZ gene in Escherichia coli. , 1987, The EMBO journal.

[98]  M. Grunberg‐Manago,et al.  AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[99]  S. Ishii,et al.  Molecular cloning and nucleotide sequencing of the nusB gene of E. coli. , 1984, Nucleic acids research.

[100]  H. A. Boer,et al.  Mutagenesis of the three bases preceding the start codon of the beta‐galactosidase mRNA and its effect on translation in Escherichia coli. , 1984, The EMBO journal.

[101]  D. Kahn,et al.  Properties and specificity of methionyl-tRNAfMet formyltransferase from Escherichia coli. , 1984, Methods in enzymology.

[102]  C. Kurland,et al.  Codon‐specific missense errors in vivo. , 1983, The EMBO journal.

[103]  H. Heyneker,et al.  Targeted random mutagenesis: the use of ambiguously synthesized oligonucleotides to mutagenize sequences immediately 5' of an ATG initiation codon. , 1983, Nucleic acids research.

[104]  M. Kozak.  Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. , 1983, Microbiological reviews.

[105]  T. D. Schneider,et al.  Characterization of Translational Initiation Sites in E. Coui , 1982 .

[106]  M Grunberg-Manago,et al.  Sequence of a 1.26‐kb DNA fragment containing the structural gene for E.coli initiation factor IF3: presence of an AUU initiator codon. , 1982, The EMBO journal.

[107]  I. G. Young,et al.  In vitro synthesis of the respiratory NADH dehydrogenase of Escherichia coli. Role of UUG as initiation codon. , 1981, Biochemistry.

[108]  D. Belin,et al.  Temperature-sensitive mutation in the initiation codon of the rIIB gene of bacteriophage T4. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[109]  P. Farabaugh.  Sequence of the lacI gene , 1978, Nature.

[110]  J. Gallant,et al.  Mistranslation in E. coli , 1977, Cell.

[111]  J. Shine,et al.  The 3'-terminal sequence of Escherichia coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[112]  H. Goodman,et al.  Sequence of the First 175 Nucleotides from the 5′ Terminus of Qβ RNA synthesized in vitro , 1969, Nature.

[113]  B. Clark,et al.  The role of N-formyl-methionyl-sRNA in protein biosynthesis. , 1966, Journal of molecular biology.

[114]  M. Capecchi,et al.  N-formylmethionyl-sRNA as the initiator of protein synthesis. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[115]  M. Nirenberg,et al.  RNA Codewords and Protein Synthesis , 1964, Science.

[116]  C. Dunnett.  A Multiple Comparison Procedure for Comparing Several Treatments with a Control , 1955 .