Translation — the process of decoding the information in messenger RNA and forming continuous chains of amino acids to form proteins — is carried out by ribosomes.
The recent crystal structures of ribosomal subunits, together with 40 years of biochemical and genetic research, are greatly increasing our understanding of how ribosomes work.
Ribosomes consist of two subunits: one subunit (30S in bacteria and archaea, 40S in eukaryotes) decodes the mRNA, reading off the triplets of nucleotide that correspond to each amino acid; the other subunit (50S in bacteria and archaea, and 60S in eukaryotes) forms the peptide bonds.
Each subunit comprises ribosomal RNAs (rRNAs) and ribosomal proteins (r-proteins). The rRNAs seem to be responsible for most enzymatic activities, whereas the r-proteins are proposed to have largely structural roles.
In almost all organisms studied, the mature rRNAs are processed from a polycistronic precursor rRNA. During ribosome synthesis, the mature rRNA regions are covalently modified within the precursor, which is then processed to release the mature rRNAs.
Given the compact nature of ribosomal subunits, the assembly of rRNAs and r-proteins must be tightly regulated. There is a strict temporal order of assembly and rRNAs cannot be folded until late in the assembly pathway.
Recent stuctural analyses have given clear insights into the mechanisms of several antibiotics that work by interfering with bacterial, but not human, protein synthesis; and future analyses are expected to allow the development of new, design-based drugs.
Structural analyses of the large and small ribosomal subunits have allowed us to think about how they work in more detail than ever before. The mechanisms that underlie ribosomal synthesis, translocation and catalysis are now being unravelled, with practical implications for the design of antibiotics.
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Ban, N., Nissen, P., Hansen, J., Moore, P. B. & Steitz, T. A. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289, 905–920 (2000).First structure of an archaeal large ribosomal subunit with atomic resolution.
Schluenzen, F. et al. Structure of functionally activated small ribosomal subunit at 3.3 angstroms resolution. Cell 102, 615–623 (2000).
Wimberly, B. T. et al. Structure of the 30S ribosomal subunit. Nature 407, 327–339 (2000).References 2 and 3 describe the structure of a bacterial small ribosomal subunit with atomic resolution.
Yusupov, M. M. et al. Crystal structure of the ribosome at 5.5 Å resolution. Science 292, 883–896 (2001).A near atomic (0.55 nm) resolution map of an entire bacterial ribosome bound by messenger RNAs and transfer RNAs. First detailed view of the intersubunit bridges.
Stark, H. et al. Arrangement of tRNAs in pre- and posttranslocational ribosomes revealed by electron cryomicroscopy. Cell 88, 19–28 (1997).
Stark, H. et al. Visualization of elongation factor Tu on the Escherichia coli ribosome. Nature 389, 403–406 (1997).
Mueller, F. et al. The 3D arrangement of the 23S and 5S rRNA in the Escherichia coli 50S ribosomal subunit based on a cryo-electron microscopic reconstruction at 7.5 Å resolution. J. Mol. Biol. 298, 35–59 (2000).
Gabashvili, I. S. et al. Solution structure of the E. coli 70S ribosome at 11.5 Å resolution. Cell 100, 537–549 (2000).
Agrawal, R. K. et al. Direct visualization of A-, P-, and E-site transfer RNAs in the Escherichia coli ribosome. Science 271, 1000–1002 (1996).
Frank, J. et al. A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome. Nature 376, 441–444 (1995).
Mueller, F. & Brimacombe, R. A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal RNA. I. Fitting the RNA to a 3D electron microscopic map at 20 Å. J. Mol. Biol. 271, 524–544 (1997).
Ban, N. et al. A 9 Å resolution X-ray crystallographic map of the large ribosomal subunit. Cell 93, 1105–1115 (1998).
Ban, N. et al. Placement of protein and RNA structures into a 5 Å-resolution map of the 50S ribosomal subunit. Nature 400, 841–847 (1999).
Tocilj, A. et al. The small ribosomal subunit from Thermus thermophilus at 4.5 Å resolution: pattern fittings and the identification of a functional site. Proc. Natl Acad. Sci. USA 96, 14252–14257 (1999).
Cate, J. H., Yusupov, M. M., Yusupova, G. Z., Earnest, T. N. & Noller, H. F. X-ray crystal structures of 70S ribosome functional complexes. Science 285, 2095–2104 (1999).
Matadeen, R. et al. The Escherichia coli large ribosomal subunit at 7.5 Å resolution. Struct. Fold Des. 7, 1575–1583 (1999).
Ramakrishnan, V. & Moore, P. B. Atomic structures at last: the ribosome in 2000. Curr. Opin. Struct. Biol. 11, 144–154 (2001).The recent history of the ribosomal structure analysis reviewed.
Khaitovich, P., Mankin, A. S., Green, R., Lancaster, L. & Noller, H. F. Characterization of functionally active subribosomal particles from Thermus aquaticus. Proc. Natl Acad. Sci. USA 96, 85–90 (1999).
Dahlberg, A. E. The functional role of ribosomal RNA in protein synthesis. Cell 57, 525–529 (1989).
Nissen, P., Hansen, J., Ban, N., Moore, P. B. & Steitz, T. A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).The peptidyl-transferase centre is described as an RNA cage, with no proteins closer than 1.8 nm to the peptide bond to be synthesized. Peptide-bond formation is proposed to follow the rules of acid–base catalysis as described in serine proteases. The ribosome is described as a ribozyme. Also see references 35 and 36.
Agrawal, R. K. et al. Visualization of tRNA movements on the Escherichia coli 70S ribosome during the elongation cycle. J. Cell Biol. 150, 447–460 (2000).Three-dimensional cryo-electron microscopy reconstructions offering snapshot views on the principal positions occupied by transfer RNAs during elongation.
Frank, J. & Agrawal, R. K. A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406, 318–322 (2000).Three-dimensional cryo-electron microscopy analysis of bacterial ribosomes in various functional states revealed a ratchet-like rotation of the small subunit relative to the large subunit upon EF-G binding and GTP hydrolysis.
Gabashvili, I. S. et al. Major rearrangements in the 70S ribosomal 3D structure caused by a conformational switch in 16S ribosomal RNA. EMBO J. 18, 6501–6507 (1999).
Stark, H., Rodnina, M. V., Wieden, H. J., van Heel, M. & Wintermeyer, W. Large-scale movement of elongation factor G and extensive conformational change of the ribosome during translocation. Cell 100, 301–309 (2000).
Agrawal, R. K., Penczek, P., Grassucci, R. A. & Frank, J. Visualization of elongation factor G on the Escherichia coli 70S ribosome: the mechanism of translocation. Proc. Natl Acad. Sci. USA 95, 6134–6138 (1998).
Agrawal, R. K., Heagle, A. B., Penczek, P., Grassucci, R. A. & Frank, J. EF-G-dependent GTP hydrolysis induces translocation accompanied by large conformational changes in the 70S ribosome. Nature Struct. Biol. 6, 643–647 (1999).
Brodersen, D. E. et al. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103, 1143–1154 (2000).
Carter, A. P. et al. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407, 340–348 (2000).
Porse, B. T. & Garrett, R. A. Ribosomal mechanics, antibiotics, and GTP hydrolysis. Cell 97, 423–426 (1999).
Ogle, J. M. et al. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001).Insights into the decoding process. Demonstration that the geometry of the Watson–Crick base-pair interactions at the codon–anticodon is sensed by specific 16S ribosomal RNA residues upon binding of a cognate tRNA.
Muth, G. W., Ortoleva-Donnelly, L. & Strobel, S. A. A single adenosine with a neutral pKa in the ribosomal peptidyl transferase center. Science 289, 947–950 (2000).
Zhang, B. & Cech, T. R. Peptide bond formation by in vitro selected ribozymes. Nature 390, 96–100 (1997).
Zhang, B. & Cech, T. R. Peptidyl-transferase ribozymes: trans reactions, structural characterization and ribosomal RNA-like features. Chem. Biol. 5, 539–553 (1998).
Xiong, L. et al. Oxazolidinone resistance mutations in 23S rRNA of Escherichia coli reveal the central region of domain V as the primary site of drug action. J. Bacteriol. 182, 5325–5331 (2000).
Polacek, N., Gaynor, M., Yassin, A. & Mankin, A. S. Ribosomal peptidyl transferase can withstand mutations the putative catalytic residue. Nature 411, 498–501 (2001).Site-directed mutagenesis on ribosomal-RNA residues proposed to be involved in peptide-bond catalysis. The rRNA is proposed to position the reacting groups without directly participating in chemical catalysis.
Barta, A. et al. Mechanism of ribosomal peptide bond formation. Science 291, 203 (2001).Three short letters present a lively discussion of the current understanding of the peptidyl-transferase reaction.
Pugh, G. E., Nicol, S. M. & Fuller-Pace, F. V. Interaction of the Escherichia coli DEAD box protein DbpA with 23S ribosomal RNA. J. Mol. Biol. 292, 771–778 (1999).
Dammel, C. S. & Noller, H. F. A cold-sensitive mutation in 16S rRNA provides evidence for helical switching in ribosome assembly. Genes Dev. 7, 660–670 (1993).
Colley, A., Beggs, J. D., Tollervey, D. & Lafontaine, D. L. Dhr1p, a putative DEAH-box RNA helicase, is associated with the box C+D snoRNP U3. Mol. Cell. Biol. 20, 7238–7246 (2000).
Daugeron, M. C. & Linder, P. Characterization and mutational analysis of yeast Dbp8p, a putative RNA helicase involved in ribosome biogenesis. Nucleic Acids Res. 29, 1144–1155 (2001).
de la Cruz, J., Kressler, D. & Linder, P. Unwinding RNA in Saccharomyces cerevisiae: DEAD-box proteins and related families. Trends Biochem. Sci. 24, 192–198 (1999).
Traub, P. & Nomura, M. Structure and function of E. coli ribosomes. V. Reconstitution of functionally active 30S ribosomal particles from RNA and proteins. Proc. Natl Acad. Sci. USA 59, 777–784 (1968).
Nomura, M. & Erdmann, V. A. Reconstitution of 50S ribosomal subunits from dissociated molecular components. Nature 228, 744–748 (1970).
Culver, G. M. & Noller, H. F. Efficient reconstitution of functional Escherichia coli 30S ribosomal subunits from a complete set of recombinant small subunit ribosomal proteins. RNA 5, 832–843 (1999).
Herold, M. & Nierhaus, K. H. Incorporation of six additional proteins to complete the assembly map of the 50S subunit from Escherichia coli ribosomes. J. Biol. Chem. 262, 8826–8833 (1987).
Agalarov, S. C., Sridhar Prasad, G., Funke, P. M., Stout, C. D. & Williamson, J. R. Structure of the S15,S6,S18-rRNA complex: assembly of the 30S ribosome central domain. Science 288, 107–113 (2000).Insights into the assembly of the small ribosomal subunit. The binding of protein S15 to the central domain of 16S ribosomal RNA is found to induce and stabilize a structural reorganization of the rRNA necessary for binding of subsequent r-proteins.
Gomez-Lorenzo, M. G. et al. Three-dimensional cryo-electron microscopy localization of EF2 in the Saccharomyces cerevisiae 80S ribosome at 17.5 Å resolution. EMBO J. 19, 2710–2718 (2000).
Ibba, M. & Soll, D. Quality control mechanisms during translation. Science 286, 1893–1897 (1999).
Nissen, P., Kjeldgaard, M. & Nyborg, J. Macromolecular mimicry. EMBO J. 19, 489–495 (2000).
Fourmy, D., Yoshizawa, S. & Puglisi, J. D. Paromomycin binding induces a local conformational change in the A-site of 16S rRNA. J. Mol. Biol. 277, 333–345 (1998).
Pioletti, M. et al. Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3. EMBO J. 20, 1829–1839 (2001).
Belova, L., Tenson, T., Xiong, L., McNicholas, P. M. & Mankin, A. S. A novel site of antibiotic action in the ribosome: interaction of evernimicin with the large ribosomal subunit. Proc. Natl Acad. Sci. USA 98, 3726–3731 (2001).
Heffron, S. E. & Jurnak, F. Structure of an EF-Tu complex with a thiazolyl peptide antibiotic determined at 2.35 Å resolution: atomic basis for GE2270A inhibition of EF-Tu. Biochemistry 39, 37–45 (2000).
Vogeley, L., Palm, G. J., Mesters, J. R. & Hilgenfeld, R. Conformational change of elongation factor Tu (EF-Tu) induced by antibiotic binding. Crystal structure of the complex between EF-Tu. GDP and aurodox. J. Biol. Chem. 276, 17149–17155 (2001).
Lafontaine, D. L. & Tollervey, D. Birth of the snoRNPs: the evolution of the modification-guide snoRNAs. Trends Biochem. Sci. 23, 383–388 (1998).
Stage-Zimmermann, T., Schmidt, U. & Silver, P. A. Factors affecting nuclear export of the 60S ribosomal subunit in vivo. Mol. Biol. Cell 11, 3777–3789 (2000).
Ho, J. H., Kallstrom, G. & Johnson, A. W. Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit. J. Cell Biol. 151, 1057–1066 (2000).
Gadal, O. et al. Nuclear export of 60S ribosomal subunits depends on Xpo1p and requires a NES-containing factor Nmd3p that associates with the large subunit protein Rpl10p. Mol. Cell. Biol. 21, 3405–3415 (2001).
Moy, T. I. & Silver, P. A. Nuclear export of the small ribosomal subunit requires the ran-GTPase cycle and certain nucleoporins. Genes Dev. 13, 2118–2133 (1999).
Kressler, D., Linder, P. & de La Cruz, J. Protein trans-acting factors involved in ribosome biogenesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 19, 7897–7912 (1999).
Venema, J. & Tollervey, D. Ribosome synthesis in Saccharomyces cerevisiae. Annu. Rev. Genet. 33, 261–311 (1999).
Li, Z., Pandit, S. & Deutscher, M. P. RNase G (CafA protein) and RNase E are both required for the 5′ maturation of 16S ribosomal RNA. EMBO J. 18, 2878–2885 (1999).
Li, Z., Pandit, S. & Deutscher, M. P. Maturation of 23S ribosomal RNA requires the exoribonuclease RNase T. RNA 5, 139–146 (1999).
Deutscher, M. P. & Li, Z. Exoribonucleases and their multiple roles in RNA metabolism. Prog. Nucleic Acid Res. Mol. Biol. 66, 67–105 (2000).
This work was supported by the Wellcome Trust. D.L.J.L. was supported by the Fonds National de la Recherche Scientifique Belge (FNRS).
- ACID–BASE CATALYSIS
A Brønsted–Lowry acid is a substance that donates a proton (hydrogen ion, H+); a Brønsted–Lowry base is a substance that accepts a proton.
- ACID-DISSOCIATION CONSTANT
(Ka). The strength of a given acid (its ability to donate a proton in water) is expressed by its acidity constant (Ka). A stronger acid has a higher Ka.
- CARBONYL GROUP
C=O; an important functional group in organic chemistry.
Mechanism by which enols and ketones rapidly interconvert. The keto–enol equilibrium usually favours the ketone product, and enols are rarely isolated. In Fig. 1b, the ketone form is on the left and the unusual enol tautomer is on the right.
- POLYCISTRONIC RNA
An RNA transcript that contains the sequence of more than one functional RNA.
- RNA HELICASES
A large, highly conserved family of RNA-dependent ATPases, generally thought to catalyse rearrangements in RNA structure. Some members can separate a base-paired RNA helix.
- EXTERNAL AND INTERNAL TRANSCRIBED SPACERS
(ETS and ITS). Regions of the ribosomal RNA precursors that do not form parts of the mature rRNAs or ribosomes, and are removed by processing.
- SMALL NUCLEOLAR RNAS
(snoRNAs). A set of small, stable RNAs, from 60 to 600 nucleotides in size. Most species form base-paired interactions with the pre-ribosomal RNAs that select sites of modification of the rRNAs. A smaller number (including U3) are required for processing of the pre-rRNA.
- TERTIARY INTERACTIONS
In addition to stem structures formed by base pairing, RNAs can interact using alternative interactions between nucleotides. These are important in the overall folding of RNA molecules, and are collectively known as tertiary interactions.
- SMALL NUCLEOLAR RIBONUCLEOPROTEINS
(snoRNPs). Complexes between the snoRNAs and specific proteins.
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Lafontaine, D., Tollervey, D. The function and synthesis of ribosomes. Nat Rev Mol Cell Biol 2, 514–520 (2001). https://doi.org/10.1038/35080045
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