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The function and synthesis of ribosomes

Key Points

  • 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.

Abstract

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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Figure 1: Peptide bond formation.
Figure 2: Conserved organization of the pre-rRNA.
Figure 3: Conserved features of pre-rRNA processing in bacteria and eukaryotes.

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Acknowledgements

This work was supported by the Wellcome Trust. D.L.J.L. was supported by the Fonds National de la Recherche Scientifique Belge (FNRS).

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DATABASE LINKS

EF-Tu

Rex1

Rex2

Rat1

Xrn1

Crm1

Rpl10

Nmd3

FURTHER INFORMATION

Tollervey lab

Glossary

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.

TAUTOMERISM

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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