In molecular biology
, translation is the process in which ribosomes
in the cytoplasm
or endoplasmic reticulum
synthesize proteins after the process of transcription
in the cell's nucleus
. The entire process is called gene expression
In translation, messenger RNA (mRNA)
is decoded in a ribosome, outside the nucleus, to produce a specific amino acid
chain, or polypeptide
. The polypeptide later folds
into an active
protein and performs its functions in the cell.
facilitates decoding by inducing the binding of complementary 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.
Translation proceeds in three phases:
# Initiation: The ribosome assembles around the target mRNA. The first tRNA is attached at the start codon
# Elongation: The last tRNA validated by the small ribosomal subunit
(''accommodation'') transfers the amino acid it carries to the large ribosomal subunit
which binds it to the one of the precedingly admitted tRNA (''transpeptidation''). The ribosome then moves to the next mRNA codon to continue the process (''translocation''), creating an amino acid chain.
# Termination: When a stop codon is reached, the ribosome releases the polypeptide.
(bacteria and archaea), translation occurs in the cytoplasm, where the large and small subunits of the ribosome
bind to the mRNA. In eukaryotes
, translation occurs in the cytosol
or across the membrane of the endoplasmic reticulum
in a process called co-translational translocation
. In co-translational translocation, the entire ribosome/mRNA complex binds to the outer membrane of the rough endoplasmic reticulum
(ER) and the new protein is synthesized and released into the ER; the newly created polypeptide can be stored inside the ER for future vesicle
transport and secretion
outside the cell, or immediately secreted.
Many types of transcribed RNA, such as transfer RNA, ribosomal RNA, and small nuclear RNA, do not undergo translation into proteins.
A number of antibiotic
s act by inhibiting translation. These include anisomycin
, and puromycin
. Prokaryotic ribosomes have a different structure from that of eukaryotic ribosomes, and thus antibiotics can specifically target bacterial infections
without any harm to a eukaryotic host's
. tRNAs are colored dark blue.
[[Image:TRNA-Phe yeast 1ehz.png|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''
The basic process of protein production is addition of one [[amino acid at a time to the end of a protein. This operation is performed by a [[ribosome. A ribosome is made up of two subunits, a small subunit and a large subunit. These subunits come together before translation of mRNA into a protein to provide a location for translation to be carried out and a polypeptide to be produced. The choice of amino acid type to add is determined by an mRNA
molecule. Each amino acid added is matched to a three nucleotide subsequence of the mRNA. For each such triplet possible, the corresponding amino acid is accepted. The successive amino acids added to the chain are matched to successive nucleotide triplets in the mRNA. In this way the sequence of nucleotides in the template mRNA chain determines the sequence of amino acids in the generated amino acid chain.
Addition of an amino acid occurs at the C-terminus
of the peptide and thus translation is said to be amino-to-carboxyl directed.
The mRNA carries genetic
information encoded as a ribonucleotide sequence from the chromosomes to the ribosomes. The ribonucleotides are "read" by translational machinery in a sequence of nucleotide
triplets called codons. Each of those triplets codes for a specific amino acid
molecules translate this code to a specific sequence of amino acids. The ribosome is a multisubunit structure containing rRNA
and proteins. It is the "factory" where amino acids are assembled into proteins.
tRNAs are small noncoding RNA chains (74–93 nucleotides) that transport amino acids to the ribosome. tRNAs have a site for amino acid attachment, and a site called an anticodon. The anticodon is an RNA triplet complementary to the mRNA triplet that codes for their cargo amino acid
Aminoacyl tRNA synthetase
s) catalyze the bonding between specific tRNA
s and the amino acids
that their anticodon sequences call for. The product of this reaction is an aminoacyl-tRNA
. In bacteria, this aminoacyl-tRNA is carried to the ribosome by EF-Tu
, where mRNA codons are matched through complementary base pair
ing to specific tRNA
anticodons. Aminoacyl-tRNA synthetases that mispair tRNAs with the wrong amino acids can produce mischarged aminoacyl-tRNAs, which can result in inappropriate amino acids at the respective position in protein. This "mistranslation" 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 ribosome has three sites for tRNA to bind. They are the aminoacyl site (abbreviated A), the peptidyl site (abbreviated P) and the exit site (abbreviated E). With respect to the mRNA, the three sites are oriented 5’ to 3’ E-P-A, because ribosomes move toward the 3' end of mRNA. The A-site
binds the incoming tRNA with the complementary codon on the mRNA. The P-site
holds the tRNA with the growing polypeptide chain. The E-site
holds the tRNA without its amino acid. When an aminoacyl-tRNA initially binds to its corresponding codon on the mRNA, it is in the A site. Then, a peptide bond forms between the amino acid of the tRNA in the A site and the amino acid of the charged tRNA in the P site. The growing polypeptide chain is transferred to the tRNA in the A site. Translocation occurs, moving the tRNA in the P site, now without an amino acid, to the E site; the tRNA that was in the A site, now charged with the polypeptide chain, is moved to the P site. The tRNA in the E site leaves and another aminoacyl-tRNA enters the A site to repeat the process.
After the new amino acid is added to the chain, and after the mRNA is released out of the nucleus and into the ribosome's core, the energy provided by the hydrolysis of a GTP bound to the translocase EF-G
) and a/eEF-2
) moves the ribosome down one codon towards the 3' end
. The energy required for translation of proteins is significant. For a protein containing ''n'' amino acids, the number of high-energy phosphate bonds required to translate it is 4''n''-1 . The rate of translation varies; it is significantly higher in prokaryotic cells (up to 17–21 amino acid residues per second) than in eukaryotic cells (up to 6–9 amino acid residues per second).
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. The rate of error in synthesizing proteins has been estimated to be between 1/105
misincorporated amino acids, depending on the experimental conditions. The rate of premature translation abandonment, instead, has been estimated to be of the order of magnitude of 10−4
events per translated codon.
The correct amino acid is covalently bonded
to the correct transfer RNA (tRNA)
by amino acyl transferases. The amino acid is joined by its carboxyl group to the 3' OH of the tRNA by an ester bond
. When the tRNA has an amino acid linked to it, the tRNA is termed "charged". Initiation involves the small subunit of the ribosome binding to the 5' end of mRNA with the help of initiation factors
(IF). In bacteria and a minority of archaea, initiation of protein synthesis involves the recognition of a purine-rich initiation sequence on the mRNA called the Shine-Delgarno sequence. The Shine-Delgarno sequence binds to a complementary pyrimidine-rich sequence on the 3' end of the 16S rRNA part of the 30S ribosomal subunit. 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. Once the mRNA and 30S subunit are properly bound, an initiation factor brings the initiator tRNA-amino acid complex, f-Met-tRNA, to the 30S P site. The initiation phase is completed once a 50S subunit joins the 30 subunit, forming an active 70S ribosome.
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. tRNA usually cannot recognize or bind to stop codons. Instead, the stop codon induces the binding of a release factor
protein. (RF1 & RF2) that prompts the disassembly of the entire ribosome/mRNA complex by the hydrolysis of the polypeptide chain from the peptidyl transferase center of the ribosome 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. In such cases of 'translational readthrough', translation continues until the ribosome encounters the next stop codon.
The process of translation is highly regulated in both eukaryotic and prokaryotic organisms. Regulation of translation can impact the global rate of protein synthesis which is closely coupled to the metabolic and proliferative state of a cell. In addition, recent work has revealed that genetic differences and their subsequent expression as mRNAs can also impact translation rate in an RNA-specific manner.
Translational control is critical for the development and survival of cancer
. Cancer cells must frequently regulate the translation phase of gene expression, though it is not fully understood why translation is targeted over steps like transcription. While cancer cells often have genetically altered translation factors, it is much more common for cancer cells to modify the levels of existing translation factors.
Several major oncogenic signaling pathways, including the RAS–MAPK
, MYC, and WNT–β-catenin
pathways, ultimately reprogram the genome via translation. Cancer cells also control translation to adapt to cellular stress. During stress, the cell translates mRNAs that can mitigate the stress and promote survival. An example of this is the expression of AMPK
in various cancers; its activation triggers a cascade that can ultimately allow the cancer to escape apoptosis
(programmed cell death) triggered by nutrition deprivation. Future cancer therapies may involve disrupting the translation machinery of the cell to counter the downstream effects of cancer.
Mathematical modeling of translation
500 px|Figure M1'. The extended model of protein synthesis ''M1'' with explicit presentation of 40S, 60S and initiation factors (IF) binding.
The transcription-translation process description, mentioning only the most basic ”elementary” processes, consists of:
# production of mRNA molecules (including splicing),
# initiation of these molecules with help of initiation factors (e.g., the initiation can include the circularization step though it is not universally required),
# initiation of translation, recruiting the small ribosomal subunit,
# assembly of full ribosomes,
# elongation, (i.e. movement of ribosomes along mRNA with production of protein),
# termination of translation,
# degradation of mRNA molecules,
# degradation of proteins.
The process of protein synthesis and translation is a subject of mathematical modeling for a long time starting from the first detailed kinetic models such as
or others taking into account stochastic aspects of translation and using computer simulations. Many chemical kinetics-based models of protein synthesis have been developed and analyzed in the last four decades.
Beyond chemical kinetics, various modeling formalisms such as Totally Asymmetric Simple Exclusion Process (TASEP)
Probabilistic Boolean Networks (PBN)
, Petri Nets
and max-plus algebra
have been applied to model the detailed kinetics of protein synthesis or some of its stages. A basic model of protein synthesis that took into account all eight 'elementary' processes has been developed,
following the paradigm
that "useful models
are simple and extendable".
The simplest model ''M0'' is represented by the reaction kinetic mechanism (Figure M0). It was generalised to include 40S, 60S and initiation factor
s (IF) binding (Figure M1'). It was extended further to include effect of microRNA
on protein synthesis.
Most of models in this hierarchy can be solved analytically. These solutions were used to extract 'kinetic signatures' of different specific mechanisms of synthesis regulation.
Whereas other aspects such as the 3D structure, called tertiary structure
, of protein can only be predicted using sophisticated algorithms
, the amino acid sequence, called primary structure
, can be determined solely from the nucleic acid sequence with the aid of a translation table
This approach may not give the correct amino acid composition of the protein, in particular if unconventional amino acid
s 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).
There are many computer programs capable of translating a DNA/RNA sequence into a protein sequence. 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. For instance, the rare alternative start codon CTG codes for Methionine
when used as a start codon, and for Leucine
in all other positions.
Example: Condensed translation table for the Standard Genetic Code (from thNCBI Taxonomy webpage
AAs = FFLLSSSSYY**CC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
Starts = ---M---------------M---------------M----------------------------
Base1 = TTTTTTTTTTTTTTTTCCCCCCCCCCCCCCCCAAAAAAAAAAAAAAAAGGGGGGGGGGGGGGGG
Base2 = TTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGG
Base3 = TCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAG
The "Starts" row indicate three start codons, UUG, CUG, and the very common AUG. It also indicates the first amino acid residue when interpreted as a start: in this case it is all methionine.
Even when working with ordinary eukaryotic sequences such as the Yeast
genome, it is often desired to be able to use alternative translation tables—namely for translation of the mitochondrial genes. Currently the following translation tables are defined by the NCBI
Taxonomy Group for the translation of the sequences in GenBank
# The standard code
# The vertebrate mitochondrial code
# The yeast mitochondrial code
# The mold, protozoan, and coelenterate mitochondrial code and the mycoplasma/spiroplasma code
# The invertebrate mitochondrial code
# The ciliate, dasycladacean and hexamita nuclear code
# The kinetoplast code
# The echinoderm and flatworm mitochondrial code
# The euplotid nuclear code
# The bacterial, archaeal and plant plastid code
# The alternative yeast nuclear code
# The ascidian mitochondrial code
# The alternative flatworm mitochondrial code
# The ''Blepharisma'' nuclear code
# The chlorophycean mitochondrial code
# The trematode mitochondrial code
# The ''Scenedesmus obliquus'' mitochondrial code
# The ''Thraustochytrium'' mitochondrial code
# The Pterobranchia mitochondrial code
# The candidate division SR1 and gracilibacteria code
# The ''Pachysolen tannophilus'' nuclear code
# The karyorelict nuclear code
# The ''Condylostoma'' nuclear code
# The ''Mesodinium'' nuclear code
# The peritrich nuclear code
# The ''Blastocrithidia'' nuclear code
# The Cephalodiscidae mitochondrial code
* Cell (biology)
* Cell division
* DNA codon table
* Expanded genetic code
* Gene expression
* Gene regulation
* Protein methods
* Start codon
Virtual Cell Animation Collection: Introducing Translation
Translate tool (from DNA or RNA sequence)