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Sense and nonsense recognition by the ribosome

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Book cover Ribosomes

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Abstract

Translation is the molecular process that deciphers the language of nucleic acid (nucleotides)into the language of proteins (amino acids). As for other core molecular processes, in vitro reconstituted systems have been used to define key cellular components involved in translation. During the past decade or so, there has been an explosion of ribosomal structural information defining multiple functional states throughout the translation process. These unprecedented views have allowed for the formulation of detailed hypotheses concerning the molecular mechanisms of translation, though their evaluation relies on methodologies that can observe its dynamic nature. Our laboratory has been interested in a central molecular recognition process on the ribosome — how are substrates selected that correspond to the codon poised in the A site? This question is an interesting one because this process involves two remote functional centers that span across the subunit interface of the ribosome, and as such, necessarily involves long-range signal transduction. Here we detail in broad strokes some of our contributions, mostly obtained from biochemical approaches, while placing them in the context of the field. We note that this chapter is not intended as a comprehensive overview of the field.

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References

  • Ali IK, Lancaster L, Feinberg J, Joseph S, Noller HF (2006) Deletion of a conserved, central ribosomal intersubunit RNA bridge. Mol Cell 23: 865–874

    Article  PubMed  CAS  Google Scholar 

  • Amort M, Wotzel B, Bakowska-Zywicka K, Erlacher MD, Micura R, Polacek N (2007) An intact ribose moiety at A2602 of 23S rRNA is key to trigger peptidyl-tRNA hydrolysis during translation termination. Nucleic Acids Res 35: 5130–5140

    Article  PubMed  CAS  Google Scholar 

  • Brunelle JL, Shaw JJ, Youngman EM, Green R (2008) Peptide release on the ribosome depends critically on the 2′ OH of the peptidyl-tRNA substrate. RNA 14: 1526–1531

    Article  PubMed  CAS  Google Scholar 

  • Brunelle JL, Youngman EM, Sharma D, Green R (2006) The interaction between C75 of tRNA and the A loop of the ribosome stimulates peptidyl transferase activity. RNA 12: 33–39

    Article  PubMed  CAS  Google Scholar 

  • Caskey CT, Beaudet AL, Scolnick EM, Rosman M (1971) Hydrolysis of fMet-tRNA by peptidyl transferase. Proc Natl Acad Sci USA 68: 3163–3167

    Article  PubMed  CAS  Google Scholar 

  • Cochella L, Brunelle JL, Green R (2007) Mutational analysis reveals two independent molecular requirements during transfer RNA selection on the ribosome. Nat Struct Mol Biol 14: 30–36

    Article  PubMed  CAS  Google Scholar 

  • Cochella L, Green R (2005) An active role for tRNA in decoding beyond codon: anticodon pairing. Science 308: 1178–1180

    Article  PubMed  CAS  Google Scholar 

  • Erlacher MD, Lang K, Shankaran N, Wotzel B, Huttenhofer A, Micura R, Mankin AS, Polacek N (2005) Chemical engineering of the peptidyl transferase center reveals an important role of the 2′-hydroxyl group of A2451. Nucleic Acids Res 33: 1618–1627

    Article  PubMed  CAS  Google Scholar 

  • Erlacher MD, Lang K, Wotzel B, Rieder R, Micura R, Polacek N (2006) Efficient ribosomal peptidyl transfer critically relies on the presence of the ribose 2′-OH at A2451 of 23S rRNA. J Am Chem Soc 128: 4453–4459

    Article  PubMed  CAS  Google Scholar 

  • Freistroffer DV, Kwiatkowski M, Buckingham RH, Ehrenberg M (2000) The accuracy of codon recognition by polypeptide release factors. Proc Natl Acad Sci USA 97: 2046–2051

    Article  PubMed  CAS  Google Scholar 

  • Gromadski KB, Rodnina MV (2004) Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. Mol Cell 13: 191–200

    Article  PubMed  CAS  Google Scholar 

  • He SL, Green R (2010) Visualization of codon-dependent conformational rearrangements during translation termination. Nat Struct Mol Biol 17: 465–470

    Article  PubMed  CAS  Google Scholar 

  • Hopfield JJ (1974) Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci USA 71: 4135–4139

    Article  PubMed  CAS  Google Scholar 

  • Ito K, Uno M, Nakamura Y (2000) A tripeptide ‘anticodon’ deciphers stop codons in messenger RNA. Nature 403: 680–684

    Article  PubMed  CAS  Google Scholar 

  • Jenner L, Demeshkina N, Yusupova G, Yusupov M (2010) Structural rearrangements of the ribosome at the tRNA proofreading step. Nat Struct Mol Biol (Epub ahead of print)

    Google Scholar 

  • Jorgensen F, Adamski FM, Tate WP, Kurland CG (1993) Release factor-dependent false stops are infrequent in Escherichia coli. J Mol Biol 230: 41–50

    Article  PubMed  CAS  Google Scholar 

  • Koch M, Huang Y, Sprinzl M (2008) Peptide-bond synthesis on the ribosome: no free vicinal hydroxy group required on the terminal ribose residue of peptidyl-tRNA. Angew Chem Int ed 47: 7242–7245

    Article  CAS  Google Scholar 

  • Korostelev A, Asahara H, Lancaster L, Laurberg M, Hirschi A, Zhu J, Trakhanov S, Scott WG, Noller HF (2008) Crystal structure of a translation termination complex formed with release factor RF2. Proc Natl Acad Sci USA 105: 19684–19689

    Article  PubMed  Google Scholar 

  • Laurberg M, Asahara H, Korostelev A, Zhu J, Trakhanov S, Noller HF (2008) Structural basis for translation termination on the 70S ribosome. Nature 454: 852–857

    Article  PubMed  CAS  Google Scholar 

  • Ledoux S, Olejniczak M, Uhlenbeck OC (2009) A sequence element that tunes Escherichia coli tRNA(Ala)(GGC) to ensure accurate decoding. Nat Struct Mol Biol 16: 359–364

    Article  PubMed  CAS  Google Scholar 

  • Li W, Agirrezabala X, Lei J, Bouakaz L, Brunelle JL, Ortiz-Meoz RF, Green R, Sanyal S, Ehrenberg M, Frank J (2008) Recognition of aminoacyl-tRNA: a common molecular mechanism revealed by cryo-EM. EMBO J 27: 3322–3331

    Article  PubMed  CAS  Google Scholar 

  • Mora L, Zavialov A, Ehrenberg M, Buckingham RH (2003) Stop codon recognition and interactions with peptide release factor RF3 of truncated and chimeric RF1 and RF2from Escherichia coli. Mol Microbiol 50: 1467–1476

    Article  PubMed  CAS  Google Scholar 

  • Murphy FV 4th, Ramakrishnan V (2004) Structure of a purine-purine wobble base pair in the decoding center of the ribosome. Nat Struct Mol Biol 11: 1251–1252

    Article  PubMed  CAS  Google Scholar 

  • O’Connor M (2009) Helix 69 in 23S rRNA modulates decoding by wild type and suppressor tRNAs. Mol Genet Genomics 282: 371–380

    Article  CAS  Google Scholar 

  • O’Connor M, Dahlberg AE (1995) The involvement of two distinct regions of 23 S ribosomal RNA in tRNA selection. J Mol Biol 254: 838–847

    Article  CAS  Google Scholar 

  • Ogle JM, Brodersen DE, Clemons WM, Jr., Tarry MJ, Carter AP, Ramakrishnan V (2001) Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292: 897–902

    Article  PubMed  CAS  Google Scholar 

  • Ogle JM, Murphy FV, Tarry MJ, Ramakrishnan V (2002) Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell 111: 721–732

    Article  PubMed  CAS  Google Scholar 

  • Ortiz-Meoz R, Green R (2010) Functional elucidation of a key contact between tRNA and the large ribosomal subunit rRNA during decoding. RNA 16: 2002–2013

    Article  PubMed  CAS  Google Scholar 

  • Pan D, Zhang CM, Kirillov S, Hou YM, Cooperman BS (2008) Perturbation of the tRNA tertiary core differentially affects specific steps of the elongation cycle. J Biol Chem 283: 18 431–18440

    CAS  Google Scholar 

  • Pape T, Wintermeyer W, Rodnina M (1999) Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. EMBO J 18: 3800–3807

    Article  PubMed  CAS  Google Scholar 

  • Pape T, Wintermeyer W, Rodnina MV (1998) Complete kinetic mechanism of elongation factor Tu-dependent binding of aminoacyl-tRNA to the A site of the E. coli ribosome. EMBO J 17: 7490–7497

    Article  PubMed  CAS  Google Scholar 

  • Pape T, Wintermeyer W, Rodnina MV (2000) Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome. Nat Struct Biol 7: 104–107

    Article  PubMed  CAS  Google Scholar 

  • Piepenburg O, Pape T, Pleiss JA, Wintermeyer W, Uhlenbeck OC, Rodnina MV (2000) Intact aminoacyl-tRNA is required to trigger GTP hydrolysis by elongation factor Tu on the riboome. Biochemistry 39: 1734–1738

    Article  PubMed  CAS  Google Scholar 

  • Polacek N, Gomez MJ, Ito K, Xiong L, Nakamura Y, Mankin A (2003) The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. Mol Cell 11: 103–112

    Article  PubMed  CAS  Google Scholar 

  • Saarma U, Remme J, Ehrenberg M, Bilgin N (1997) An A to U transversion at position 1067 of 23 S rRNA from Escherichia coli impairs EF-Tu and EF-G function. J Mol Biol 272: 327–335

    Article  PubMed  CAS  Google Scholar 

  • Schmeing TM, Huang KS, Kitchen DE, Strobel SA, Steitz TA (2005a) Structural insights into the roles of water and the 2′ hydroxyl of the P site tRNA in the peptidyl transferase reaction. Mol Cell 20: 437–448

    Article  PubMed  CAS  Google Scholar 

  • Schmeing TM, Huang KS, Strobel SA, Steitz TA (2005b) An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438: 520–524

    Article  PubMed  CAS  Google Scholar 

  • Schmeing TM, Ramakrishnan V (2009) What recent ribosome structures have revealed about the mechanism of translation. Nature 461: 1234–1242

    Article  PubMed  CAS  Google Scholar 

  • Schmeing TM, Voorhees RM, Kelley AC, Gao YG, Murphy FV 4th, Weir JR, Ramakrishnan V (2009) The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science 326: 688–694

    Article  PubMed  CAS  Google Scholar 

  • Seit-Nebi A, Frolova L, Justesen J, Kisselev L (2001) Class-1 translation termination factors: invariant GGQ minidomain is essential for release activity and ribosome binding but not for stop codon recognition. Nucleic Acids Res 29: 3982–3987

    PubMed  CAS  Google Scholar 

  • Shaw JJ, Green R (2007) Two distinct components of release factor function uncovered by nucleophile partitioning analysis. Mol Cell 28: 458–467

    Article  PubMed  CAS  Google Scholar 

  • Stark H, Rodnina MV, Wieden HJ, Zemlin F, Wintermeyer W, van Heel M (2002) Ribosome interactions of aminoacyl-tRNA and elongation factor Tu in the codon-recognition complex. Nat Struct Biol 9: 849–854

    PubMed  CAS  Google Scholar 

  • Thompson RC, Stone PJ (1977) Proofreading of the codon-anticodon interaction on ribosomes. Proc Natl Acad Sci USA 74: 198–202

    Article  PubMed  CAS  Google Scholar 

  • Valle M, Sengupta J, Swami NK, Grassucci RA, Burkhardt N, Nierhaus KH, Agrawal K, Frank J (2002) Cryo-EM reveals an active role for aminoacyl-tRNA in the accommodation process. EMBO J 21: 3557–3567

    Article  PubMed  CAS  Google Scholar 

  • Vestergaard B, Sanyal S, Roessle M, Mora L, Buckingham RH, Kastrup JS, Gajhede M, Svergun DI, Ehrenberg M (2005) The SAXS solution structure of RF1 differs from its crystal structure and is similar to its ribosome bound cryo-EM structure. Mol Cell 20: 929–938

    Article  PubMed  CAS  Google Scholar 

  • Vestergaard B, Van LB, Andersen GR, Nyborg J, Buckingham RH, Kjeldgaard M (2001) Bacterial polypeptide release factor RF2 is structurally distinct from eukaryotic eRF1. Mol Cell 8: 1375–1382

    Article  PubMed  CAS  Google Scholar 

  • Weinger JS, Parnell KM, Dorner S, Green R, Strobel SA (2004) Substrate-assisted catalysis of peptide bond formation by the ribosome. Nat Struct Mol Biol 11: 1101–1106

    Article  PubMed  CAS  Google Scholar 

  • Weixlbaumer A, Jin H, Neubauer C, Voorhees RM, Petry S, Kelley AC, Ramakrishnan V (2008) Insights into translational termination from the structure of RF2 bound to the ribosome. Science 322: 953–956

    Article  PubMed  CAS  Google Scholar 

  • Youngman EM, Brunelle JL, Kochaniak AB, Green R (2004) The active site of the ribosome is composed of two layers of conserved nucleotides with distinct roles in peptide bond formation and peptide release. Cell 117: 589–599

    Article  PubMed  CAS  Google Scholar 

  • Youngman EM, He SL, Nikstad LJ, Green R (2007) Stop codon recognition by release factors induces structural rearrangement of the ribosomal decoding center that is productive for peptide release. Mol Cell 28: 533–543

    Article  PubMed  CAS  Google Scholar 

  • Zaher HS, Green R (2010a) Hyperaccurate and error-prone ribosomes exploit distinct mechanisms during tRNA selection. Mol Cell 39: 110–120

    Article  PubMed  CAS  Google Scholar 

  • Zaher H, Green R (2010b) Kinetic basis for global loss of fidelity arising from mismatches in the P-site codon: anticodon, RNA 1980–1989

    Google Scholar 

  • Zaher HS, Green R (2009 a) Fidelity at the molecular level: lessons from protein synthesis. Cell 136: 746–762

    Article  PubMed  CAS  Google Scholar 

  • Zaher HS, Green R (2009b) Quality control by the ribosome following peptide bond formation. Nature 457: 161–166

    Article  PubMed  CAS  Google Scholar 

  • Zavialov AV, Mora L, Buckingham RH, Ehrenberg M (2002) Release of peptide promoted by the GGQ motif of class-I release factors regulates the GTPase activity of RF3. Mol Cell 10: 789–798

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Rodrigo F. Ortiz-Meoz
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  2. Shan L. He
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  3. Hani S. Zaher
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  4. Rachel Green
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Editors and Affiliations

  1. Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077, Göttingen, Germany

    Marina V. Rodnina  & Wolfgang Wintermeyer  & 

  2. Howard Hughes Medical Institute Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Rachel Green

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Ortiz-Meoz, R.F., He, S.L., Zaher, H.S., Green, R. (2011). Sense and nonsense recognition by the ribosome. In: Rodnina, M.V., Wintermeyer, W., Green, R. (eds) Ribosomes. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0215-2_17

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