Translation and the Synthesis of Proteins

What translation actually produces

Translation uses the codon sequence of an mRNA to specify an ordered chain of amino acids. The chain is called a polypeptide; it may subsequently fold, be chemically modified, or combine with other chains to become a functional protein. This is different from transcription, where a nucleic-acid template determines another nucleic-acid sequence by base pairing. During translation there is no direct base–amino-acid complementarity; correctly charged tRNAs and the ribosome provide the bridge.

ATP-dependent charging prepares the building blocks

An amino acid is activated and attached to its specific tRNA by an aminoacyl-tRNA synthetase. The reaction consumes ATP and produces an aminoacyl-tRNA with a high-energy connection between amino acid and tRNA. Synthetase specificity and, for some enzymes, proofreading prevent incompatible amino acids from being delivered. It is misleading to describe a free amino acid simply attaching by itself after a tRNA sees an mRNA codon. Charging typically precedes codon recognition in the ribosome.

Ribosome structure and catalytic function

A ribosome consists of a small and a large subunit containing proteins and ribosomal RNA. The small subunit helps read mRNA codons, while the large subunit positions tRNAs and catalyses peptide-bond formation. A, P and E sites describe aminoacyl-tRNA entry, peptidyl-tRNA holding and departing tRNA, respectively. The peptidyl-transferase activity is contributed primarily by rRNA—a ribozyme—so RNA is not merely a passive message in protein synthesis.

Ribosomes do not read the DNA double helix directly. They bind messenger RNA. A bacterial ribosome differs in composition from a eukaryotic cytoplasmic ribosome, but the general coding logic and peptide-bond chemistry are highly conserved.

Initiation establishes the correct reading frame

A small ribosomal subunit, initiation factors and an initiator tRNA assemble at a suitable mRNA start site. AUG normally specifies methionine; in bacteria the initiating methionine is commonly modified to formylmethionine. The initiator tRNA is placed so the start codon defines the frame of subsequent triplets. The large ribosomal subunit joins to establish a functional translation complex. Untranslated regions before the start and after the stop codon influence how the mRNA is recognised, regulated and translated; they are transcribed but not normally converted into amino-acid sequence.

Elongation proceeds one codon at a time

A correctly charged tRNA enters the A site and pairs with the next mRNA codon. The ribosome's catalytic centre forms a peptide bond, transferring the growing polypeptide to the amino acid carried by the A-site tRNA. With elongation-factor activity, the ribosome translocates one codon along the mRNA in the 5′→3′ direction: the newly peptidyl-bearing tRNA moves toward the P site and the empty tRNA eventually leaves through E. This cycle repeats as amino acids are added to the carboxyl end of the growing polypeptide.

Termination and later protein function

When a stop codon reaches the decoding site, it is recognised by a release factor rather than a conventional charged tRNA. Release-factor activity hydrolyses the connection between the completed polypeptide and the terminal tRNA. The polypeptide is released and ribosomal components can be recycled. A correct amino-acid sequence is necessary but not always sufficient for biological function: folding, cellular location and post-translational processing also matter.

Reading a worked translation unit

Consider 5′-GGG AUG GCU UUU UAA CCA-3′. If translation starts at AUG, the codons AUG, GCU and UUU encode Met–Ala–Phe; UAA ends translation. The leading GGG and trailing CCA in this schematic are outside the translated region. Without knowing where initiation occurs, arbitrary triplet grouping from the first character could yield a meaningless answer.

A translation cycle followed by location

The ribosome has three principal sites for tRNA movement. The A site typically accepts the new aminoacyl-tRNA that matches an mRNA codon. The P site holds the tRNA attached to the growing polypeptide. After peptide-bond formation, the growing chain is transferred to the newly arrived tRNA, and translocation shifts the complex by one codon. The previously peptide-bearing, now empty tRNA passes toward the E exit site. The next charged tRNA can then enter the A site. This recurring cycle converts a sequence of RNA triplets into a directional sequence of peptide bonds.

During peptide-bond formation, the amino group on the incoming amino acid reacts with the ester linkage holding the growing chain to the P-site tRNA. The large-subunit rRNA helps position reacting groups and catalyse this chemistry. The incoming amino acid is added to the carboxyl end of the growing polypeptide; peptide synthesis therefore proceeds from the amino to the carboxyl terminus. This is a different direction convention from the 5′ and 3′ ends used for nucleic acids, even though the two directions are coordinated by the translating ribosome.

Reading an mRNA from its correct start

An mRNA may contain bases before the start codon, so grouping nucleotides into triplets beginning at the very first 5′ nucleotide is not necessarily correct. For instance, 5′-ACCAUGGCUUUUUAGG-3′ contains an AUG beginning after the initial ACC sequence. Translation initiated there gives AUG–GCU–UUU followed by UAG, producing Met–Ala–Phe before termination. The upstream ACC and downstream G are not translated in this illustrative case. This example shows why a mutation that creates or destroys a start codon can change far more than a single amino acid.

Translation termination depends on a protein release factor entering the decoding centre when the stop codon reaches it. The completed polypeptide is released and the ribosome dissociates or is recycled. Some growing proteins are delivered to particular membranes or cell compartments while translation is occurring; others are transported later. Additional molecular chaperones and modification enzymes may be needed for the chain to reach its active conformation.

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