Protein Synthesis and Translation

Protein synthesis, or translation, is the process by which the ribosome reads the sequence of a messenger RNA and assembles the corresponding chain of amino acids into a protein. It is the step that converts the genetic code into the functional molecules of the cell and is the destination for the amino acids handled elsewhere in protein and amino acid metabolism.

Definition

Translation is the ribosome-catalyzed synthesis of a polypeptide whose amino acid sequence is specified by the codons of a messenger RNA, using aminoacyl-transfer RNAs as adaptors that read the genetic code.

Scope

This entry covers how amino acids are activated and matched to codons through aminoacyl-tRNA synthesis, and the initiation, elongation, and termination phases of translation on the ribosome, together with the major points at which the process is regulated. It treats translation as a biochemical and molecular process.

Core questions

• How is each amino acid linked to the transfer RNA that recognizes its codon?
• How does the ribosome select the start site and read codons in frame?
• How is the rate of translation regulated in response to cellular conditions?

Key concepts

• Genetic code and codon-anticodon pairing
• Aminoacyl-tRNA synthetases and tRNA charging
• Ribosome and the A, P, and E sites
• Initiation, elongation, and termination
• Translation initiation factors and regulation
• Ribosome profiling as a measurement method

Mechanisms

Each amino acid is first joined to its cognate transfer RNA by an aminoacyl-tRNA synthetase, an ATP-dependent reaction whose accuracy, including proofreading, sets the fidelity of the genetic code. The charged tRNAs deliver amino acids to the ribosome, where translation proceeds in three phases. In initiation, the small ribosomal subunit, helped by initiation factors, locates the start codon, typically by scanning in eukaryotes, and the large subunit joins. In elongation, the ribosome moves codon by codon, catalyzing peptide-bond formation between successive amino acids in its peptidyl-transferase center while tRNAs cycle through its A, P, and E sites. Termination occurs when a stop codon is recognized by release factors and the completed polypeptide is freed. Initiation is the most heavily regulated phase; its control through initiation factors lets cells rapidly adjust global and message-specific protein output. Ribosome profiling allows translation to be measured genome-wide at near-codon resolution.

Clinical relevance

Translation is the target of several classes of antibiotics that exploit differences between bacterial and human ribosomes, and its regulation is altered in many disease states. This entry describes the mechanism and how it is studied, and does not provide individual treatment guidance.

Evidence & guidelines

The mechanism and its regulation are established molecular biology supported by extensive primary and review literature; this is a reference topic rather than a clinical guideline domain.

History

The genetic code was deciphered in the 1960s through the work of Marshall Nirenberg, Har Gobind Khorana, and others, while the discovery of transfer RNA as an adaptor by Mahlon Hoagland and colleagues explained how the code is read. Later structural and biochemical studies resolved the ribosome and the factors controlling each phase of translation.

Key figures

• Marshall Nirenberg
• Har Gobind Khorana
• Mahlon Hoagland
• Alan Hinnebusch

Seminal works

• ibba-soll-2000
• sonenberg-hinnebusch-2009
• jackson-2010

Frequently asked questions

What is the role of transfer RNA in translation?

Transfer RNA acts as an adaptor: each charged tRNA carries a specific amino acid and pairs its anticodon with the matching codon on the messenger RNA, so the ribosome can add the correct amino acid as it reads the code.

Why is the initiation step of translation so important for regulation?

Initiation commits the ribosome to making a protein, so controlling it through initiation factors lets the cell quickly raise or lower protein production, broadly or for specific messages, in response to its needs.