Ribosomes and Translation

Translation is the process by which the ribosome reads the codons of a messenger RNA and assembles the corresponding chain of amino acids. The ribosome is a large complex of ribosomal RNA and proteins, organised into a small subunit that decodes the mRNA and a large subunit that catalyses peptide-bond formation. Structural studies showed that this catalysis is performed by ribosomal RNA, making the ribosome a ribozyme.

Definition

Translation is the ribosome-mediated synthesis of a polypeptide, in which transfer RNAs deliver amino acids matched to successive mRNA codons and the ribosome's RNA core catalyses peptide-bond formation between them.

Scope

This topic covers the structure of the ribosome and its subunits, the three phases of translation (initiation, elongation, termination), the roles of transfer RNA and the genetic code, and the regulation of translation initiation as a control point for gene expression. It is a molecular-biology reference and gives no clinical advice.

Core questions

• How is an mRNA codon matched to the correct amino acid?
• What are the roles of the small and large ribosomal subunits?
• How are the start and stop of translation defined?
• Why is initiation the principal regulated step of translation?

Key concepts

• Small and large ribosomal subunits
• Ribosomal RNA and ribosomal proteins
• A, P, and E tRNA-binding sites
• Transfer RNA and aminoacylation
• The genetic code and codon-anticodon pairing
• Initiation, elongation, and termination
• Peptidyl transferase centre
• Cap-dependent translation initiation

Key theories

The ribosome as a ribozyme

High-resolution structures of the large subunit placed only ribosomal RNA, not protein, at the peptidyl transferase centre, supporting the view that peptide-bond formation is catalysed by RNA and consistent with an RNA-world origin of translation.

Mechanisms

A ribosome assembles on an mRNA with the small subunit positioning the start codon and an initiator tRNA; in eukaryotes this cap-dependent initiation is the major regulated step, controlled through initiation factors (Sonenberg & Hinnebusch, 2009). During elongation, aminoacyl-tRNAs enter the A site, the large subunit's peptidyl transferase centre forms the peptide bond, and the ribosome translocates so the chain grows codon by codon; structural work localised this catalytic activity to ribosomal RNA (Nissen et al., 2000). Recognition of a stop codon by release factors terminates synthesis and frees the completed polypeptide, which then folds according to its sequence (Anfinsen, 1973).

Clinical relevance

Because translation determines which proteins a cell makes and in what amounts, its regulation is central to normal cell growth, and several antibiotics act by targeting bacterial ribosomes. This entry describes the mechanism and its general significance; it is not a guide to drug selection or patient care.

History

The outline of translation, the genetic code, and the adaptor role of tRNA were established through mid-twentieth-century molecular biology. Atomic-resolution crystal structures of the ribosomal subunits around 2000, including the demonstration that RNA forms the catalytic core (Nissen et al., 2000), transformed understanding of how the ribosome works and were recognised by the 2009 Nobel Prize in Chemistry.

Key figures

• Thomas Steitz
• Venkatraman Ramakrishnan
• Ada Yonath
• Nahum Sonenberg

Seminal works

• nissen-2000
• sonenberg-2009

Frequently asked questions

What is the difference between transcription and translation?

Transcription copies a DNA gene into messenger RNA; translation reads that messenger RNA on the ribosome and builds the corresponding protein. Translation is the protein-making step.

Why is the ribosome called a ribozyme?

Because its catalytic site, which forms the peptide bonds between amino acids, is built from ribosomal RNA rather than protein, the ribosome is an RNA enzyme, or ribozyme.