Translation (biology)

In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates.

In translation, messenger RNA (mRNA) is decoded in a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide.

[1] The ribosome facilitates decoding by inducing the binding of complementary transfer RNA (tRNA) anticodon sequences to mRNA codons.

The tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is "read" by the ribosome.

In eukaryotes, translation occurs in the cytoplasm or across the membrane of the endoplasmic reticulum through a process called co-translational translocation.

[3] The choice of amino acid type to add is determined by a messenger RNA (mRNA) molecule.

[citation needed] The ribosome molecules translate this code to a specific sequence of amino acids.

Transfer RNAs (tRNAs) are small noncoding RNA chains (74–93 nucleotides) that transport amino acids to the ribosome.

Aminoacyl tRNA synthetases (enzymes) catalyze the bonding between specific tRNAs and the amino acids that their anticodon sequences call for.

In bacteria, this aminoacyl-tRNA is carried to the ribosome by EF-Tu, where mRNA codons are matched through complementary base pairing to specific tRNA anticodons.

This "mistranslation"[7] of the genetic code naturally occurs at low levels in most organisms, but certain cellular environments cause an increase in permissive mRNA decoding, sometimes to the benefit of the cell.

The binding of these complementary sequences ensures that the 30S ribosomal subunit is bound to the mRNA and is aligned such that the initiation codon is placed in the 30S portion of the P-site.

[11] Termination of the polypeptide occurs when the A site of the ribosome is occupied by a stop codon (UAA, UAG, or UGA) on the mRNA, creating the primary structure of a protein.

Instead, the stop codon induces the binding of a release factor protein[12] (RF1 & RF2) that prompts the disassembly of the entire ribosome/mRNA complex by the hydrolysis of the polypeptide chain from the peptidyl transferase center [2] of the ribosome.

[13] Drugs or special sequence motifs on the mRNA can change the ribosomal structure so that near-cognate tRNAs are bound to the stop codon instead of the release factors.

[14] Even though the ribosomes are usually considered accurate and processive machines, the translation process is subject to errors that can lead either to the synthesis of erroneous proteins or to the premature abandonment of translation, either because a tRNA couples to a wrong codon or because a tRNA is coupled to the wrong amino acid.

[15] The rate of error in synthesizing proteins has been estimated to be between 1 in 105 and 1 in 103 misincorporated amino acids, depending on the experimental conditions.

Regulation of translation can impact the global rate of protein synthesis which is closely coupled to the metabolic and proliferative state of a cell.

To study this process, scientists have used a wide variety of methods such as structural biology, analytical chemistry (mass-spectrometry based), imaging of reporter mRNA translation (in which the translation of a mRNA is linked to an output, such as luminescence or fluorescence), and next-generation sequencing based methods.

For example, research utilizing this method has revealed that genetic differences and their subsequent expression as mRNAs can also impact translation rate in an RNA-specific manner.

[21] Expanding on this concept, a more recent development is single-cell ribosome profiling, a technique that allows us to study the translation process at the resolution of individual cells.

It is also possible to translate either by hand (for short sequences) or by computer (after first programming one appropriately, see section below); this allows biologists and chemists to draw out the chemical structure of the encoded protein on paper.

This approach may not give the correct amino acid composition of the protein, in particular if unconventional amino acids such as selenocysteine are incorporated into the protein, which is coded for by a conventional stop codon in combination with a downstream hairpin (SElenoCysteine Insertion Sequence, or SECIS).

Normally this is performed using the Standard Genetic Code, however, few programs can handle all the "special" cases, such as the use of the alternative initiation codons which are biologically significant.

Overview of eukaryotic messenger RNA (mRNA) translation
Translation of mRNA and ribosomal protein synthesis
Initiation and elongation stages of translation involving RNA nucleobases , the ribosome, transfer RNA , and amino acids
The three phases of translation: (1) in initiation, the small ribosomal subunit binds to the RNA strand and the initiator tRNA–amino acid complex binds to the start codon, culminating in attachment of the large subunit; (2) elongation occurs as a cycle, in which codons are sequentially recognized by charged tRNAs, followed by peptide bond formation with transfer of the polypeptide between tRNAs within the ribosome and finally translocation of the ribosome to the next codon; (3) termination, when a stop codon is reached, a release factor binds and the polypeptide is released (note that labels for translocation and peptide bond formation are reversed in this image)
A ribosome translating a protein that is secreted into the endoplasmic reticulum (tRNAs colored dark blue)
Tertiary structure of tRNA ( CCA tail in yellow, Acceptor stem in purple, Variable loop in orange, D arm in red, Anticodon arm in blue with Anticodon in black, T arm in green)
Figure M0. Basic and the simplest model M0 of protein synthesis. Here, * M – amount of mRNA with translation initiation site not occupied by assembling ribosome, * F – amount of mRNA with translation initiation site occupied by assembling ribosome, * R – amount of ribosomes sitting on mRNA synthesizing proteins, * P – amount of synthesized proteins. [ 25 ]
Figure M1'. The extended model of protein synthesis M1 with explicit presentation of 40S, 60S and initiation factors (IF) binding. [ 25 ]