Translation

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Translation is the cellular process in which the genetic information carried by the DNA is decoded, using an RNA intermediate, into proteins. This process is also known as protein synthesis.

There are two steps in the path from genes to proteins. In the first step, called transcription, the region of the double-stranded DNA corresponding to a specific gene is copied into an RNA molecule, called messenger RNA (mRNA), by an enzyme called RNA polymerase. In the second step, called translation, the mRNA directs the assembly of amino acids in a specific sequence to form a chain of amino acids called a polypeptide. This process is accomplished by ribosomes, special amino acid-bearing RNA molecules called transfer RNAs (tRNAs), and other translation factors. The newly synthesized polypeptides form proteins, which have functional and structural roles in cells. All proteins are synthesized by this process.

The precise order of amino acids assembled during translation is determined by the order of nucleotides in the mRNA. These nucleotides are a direct copy of the linear sequence of the nucleotides in one of the two complementary DNA strands, which have been transcribed using a code in which every three bases of the RNA specify an amino acid. DNA and RNA molecules both have directionality, which is indicated by reference to either the 5′ ("five prime") end or the 3′ ("three prime") end.

The code is always read in the 5′ to 3′ direction, using adjacent, non-overlapping three-base units called codons. Since there are four different nucleotides (also called bases) in RNA (abbreviated A, C, G, and U), there are sixty-four (4³) different codons, and each codon specifies a particular amino acid. There are only twenty different amino acids, however, so many of the amino acids can be specified by more than one codon, a circumstance that is known as degeneracy. The list of mRNA codons specific for a givenamino acid is called the genetic code. The start signal, or initiation codon, for translating the mRNA is usually specified by an AUG, which codes for the amino acid methionine. Three codons (UAA, UGA, and UAG) do not specify an amino acid. Instead, these codons serve as stop signals to indicate that the end of the gene has been reached. During the translation process, they signal that no further amino acids are to be assembled.

The process of translation is carried out by ribosomes, which bind the mRNA and conduct a catalytic activity, called peptide bond formation, for joining the amino acids. The amino acids are carried to the ribosome by the tRNAs. Each tRNA has a specific amino acid attached to it and contains a nucleotide triplet called an anticodon. The anticodon recognizes a specific codon on the mRNA by pairing with it, using base-pairing rules like those used by DNA: A pairs with U and G pairs with C. For example, a tRNA with a UUU anticodon recognizes the AAA codon. The amino acid lysine is attached to this tRNA, so every time the ribosome "reads" an AAA codon, the lysine-bearing tRNA is brought in, base pairs via its anticodon to the codon, and delivers a lysine to the growing protein chain.

Mutations arise when one or more bases in the DNA is changed. When the mutated DNA is transcribed, the resulting mRNA will carry the same mutation. Then, when the mRNA is translated, the amino acid sequence of the resulting protein will be different from the original, or wild-type, sequence because the codons affected by the mutation will recruit the wrong amino acids. The resulting mutant protein may have neutral, harmful, or even beneficial effects on the individual. These changes are the basis for evolution.

The process of translation can be broken down into three stages. The first stage is initiation. In this step, a special "initiator" tRNA carrying the amino acid methionine binds to a special site on the small subunit of the ribosome (the ribosome is composed of two subunits, the small subunit and the largesubunit). The mRNA is also loaded on, and positioned so that the initiation codon (usually AUG) is base paired with the anticodon of the initiator tRNA. The large subunit then binds to the small subunit. The resulting complex of ribosome, mRNA, and methionine-bearing initiator tRNA is called an initiation complex. Formation of this complex also requires a number of helper proteins called initiation factors.

The second stage is called chain elongation. During this stage, additional amino acids are progressively added. The methionine-bearing initiator tRNA sits on a site of the ribosome called the P (peptidyl) site. A new tRNA, bearing the next amino acid is base paired via its anticodon to the next codon of the mRNA, using a site called the A (acceptor) site. This new amino acid is then attached to the amino acid carried by the P site tRNA, forming a peptide bond. This enzymatic step is carried out by the ribosome, at a site called the peptidyl-transferase center.

The tRNA that has so far been attached to the amino acid in the P site is then released through the E (exit) site, and the new tRNA, now carrying both its own amino acid and the methionine moves into the P site. The mRNA also slides three bases to bring the next codon into position at the A site. A third tRNA, again carrying a specific amino acid and recognizing the third codon of the mRNA, moves into the A site, and the cycle is repeated. As these steps are continued, the mRNA slides along the ribosome, three bases at a time, and the peptide (amino acid) chain continues to grow. As with initiation, elongation requires helper proteins, called elongation factors. Energy is also required for peptide bond formation.

The final stage of translation is termination. The signal to stop adding amino acids to the polypeptide is a stop codon (UAA, UAG, or UGA), for which there is no partner tRNA. Rather, special proteins called release factors bind to the A site of the ribosome and trigger an enzymatic reaction by the ribosome. This reaction causes the ribosome to release the polypeptide and mRNA, ending the elongation process.

At a given time, more than one ribosome may be translating a single mRNA molecule. The resulting clusters of ribosomes, which resemble beads on a string, are called polysomes.

Not all AUG codons serve as the site of initiation. Most AUGs are intended to code for methionines within the polypeptide chain. Therefore, in addition to the methionine-bearing initiator tRNA, another set of methionine-specific tRNAs are used for these internal AUG codons. The ribosome must be able to distinguish between these two kinds of AUG codons. In bacteria, additional information contained within the mRNA sequence immediately before the intended initiating AUG, called a Shine-Dalgarno sequence, helps the ribosome to recognize where it should start translating. Any AUG sequences on the 5′ side of the initiation codon are ignored. In eukaryotic cells, a different strategy is used to recognize the initiating AUG codon. The mRNA contains a special structure at its 5′ end, which helps the ribosome to attach and then to scan down the RNA molecule until it reaches the first AUG triplet. In bacteria and eukaryotes, AUG codons encountered during translation after initiation are recognized by a non-initiator methionine-bearingtRNA.

Genetic Code; Mutation; Nucleotide; Proteins; Reading Frame; Ribosome; Rna; Transcription.

Lewin, Benjamin. Genes VII. New York: Oxford University Press, 2000.

This is the complete article, containing 1,229 words (approx. 4 pages at 300 words per page).