Translation (biology)
Part of a series on |
Genetics |
---|
In
In translation,
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 preceding 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. The ribosomal complex remains intact and moves on to the next mRNA to be translated.
In
Many types of transcribed RNA, such as tRNA, ribosomal RNA, and small nuclear RNA, do not undergo a translation into proteins.
Several
Basic mechanisms
The basic process of protein production is the addition of one amino acid at a time to the end of a protein. This operation is performed by a ribosome.[1] A ribosome is made up of two subunits, a small subunit, and a large subunit. These subunits come together before the translation of mRNA into a protein to provide a location for translation to be carried out and a polypeptide to be produced.[2] The choice of amino acid type to add is determined by a messenger RNA (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.[3] The addition of an amino acid occurs at the C-terminus of the peptide; thus, translation is said to be amine-to-carboxyl directed.[4]
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.[citation needed]
The ribosome molecules translate this code to a specific sequence of amino acids. The ribosome is a multisubunit structure containing ribosomal RNA (rRNA) and proteins. It is the "factory" where amino acids are assembled into proteins.
Transfer RNAs (tRNAs) are small noncoding RNA chains (74–93 nucleotides) that transport amino acids to the ribosome. The repertoire of tRNA genes varies widely between species, with some bacteria having between 20 and 30 genes while complex eukaryotes could have thousands.[5] 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.
The ribosome has two binding sites for tRNA. They are the aminoacyl site (abbreviated A), and the peptidyl site/ exit site (abbreviated P/E). Concerning 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/E-site holds the tRNA with the growing polypeptide chain. 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/E site. The growing polypeptide chain is transferred to the tRNA in the A site. Translocation occurs, moving the tRNA to the P/E site, now without an amino acid; the tRNA that was in the A site, now charged with the polypeptide chain, is moved to the P/E site and the uncharged tRNA leaves, and another aminoacyl-tRNA enters the A site to repeat the process.[7]
After the new amino acid is added to the chain, and after the tRNA is released out of the ribosome and into the cytosol, the energy provided by the hydrolysis of a GTP bound to the
Initiation and termination of translation
Initiation involves the small subunit of the ribosome binding to the 5' end of mRNA with the help of
Errors in translation
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. [14] 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.[15] The rate of premature translation abandonment, instead, has been estimated to be of the order of magnitude of 10−4 events per translated codon.[16]
Regulation
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.
To delve deeper into this intricate process, scientists typically use a technique known as ribosome profiling.[17] This method enables researchers to take a snapshot of the translatome, showing which parts of the mRNA are being translated into proteins by ribosomes at a given time. Ribosome profiling provides valuable insights into translation dynamics, revealing the complex interplay between gene sequence, mRNA structure, and translation regulation. 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.[18]
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.[19] This is particularly significant as cells, even those of the same type, can exhibit considerable variability in their protein synthesis. Single-cell ribosome profiling has the potential to shed light on the heterogeneous nature of cells, leading to a more nuanced understanding of how translation regulation can impact cell behavior, metabolic state, and responsiveness to various stimuli or conditions.
Clinical significance
Translational control is critical for the development and survival of
Mathematical modeling of translation
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 amino acid building to create protein in translation is a subject of various physic models for a long time starting from the first detailed kinetic models such as[23] 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.[24][25] Beyond chemical kinetics, various modeling formalisms such as Totally Asymmetric Simple Exclusion Process,[25] Probabilistic Boolean Networks, 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 takes into account all eight 'elementary' processes has been developed,[22] following the paradigm that "useful models are simple and extendable".[26] The simplest model M0 is represented by the reaction kinetic mechanism (Figure M0). It was generalised to include 40S, 60S and initiation factors (IF) binding (Figure M1'). It was extended further to include effect of microRNA on protein synthesis.[27] 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.
Genetic code
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.
First, convert each template DNA base to its RNA complement (note that the complement of A is now U), as shown below. Note that the template strand of the DNA is the one the RNA is polymerized against; the other DNA strand would be the same as the RNA, but with thymine instead of uracil.
DNA -> RNA A -> U T -> A C -> G G -> C A=T-> A=U
Then split the RNA into triplets (groups of three bases). Note that there are 3 translation "windows", or
This will give the
Whereas other aspects such as the 3D structure, called
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).
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 the NCBI Taxonomy webpage).[28]
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.
Translation tables
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:[28]
- 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
See also
- Cell (biology)
- Cell division
- DNA codon table
- Epigenetics
- Expanded genetic code
- Gene expression
- Gene regulation
- Gene
- Genome
- Life
- Protein methods
- Start codon
References
- ^ PMID 34756086.
- ISBN 978-981-4581-85-1.
- ISBN 0-8053-1940-9.
- ISBN 0-7167-4684-0.
- PMID 36672768.
- PMID 25220850.
- ISBN 978-0-7167-6887-6.
- ^ "Computational Analysis of Genomic Sequences utilizing Machine Learning". scholar.googleusercontent.com. Retrieved 2022-01-12.
- PMID 6799491.
- S2CID 22038744.
- PMID 28301469.
- PMID 14651631.
- PMID 27490485.
- PMID 21930591.
- PMID 30921315.
- PMID 26935582.
- PMID 19213877.
- PMID 26297486.
- PMID 37344592.)
{{cite journal}}
: CS1 maint: multiple names: authors list (link - ^ .
- PMID 27112207.
- ^ PMID 31698578.
- S2CID 27559249.
- PMID 7442295.
- ^ S2CID 83701439.
- PMID 28341710.
- PMID 22850425.
- ^ a b Elzanowski, Andrzej; Ostell, Jim (January 2019). "The Genetic Codes". National Center for Biotechnology Information (NCBI). Retrieved 31 May 2022.
Further reading
- Champe PC, Harvey RA, Ferrier DR (2004). Lippincott's Illustrated Reviews: Biochemistry (3rd ed.). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-2265-9.
- Cox M, Nelson DR, Lehninger AL (2005). Lehninger principles of biochemistry (4th ed.). San Francisco...: W.H. Freeman. ISBN 0-7167-4339-6.
- Malys N, McCarthy JE (March 2011). "Translation initiation: variations in the mechanism can be anticipated". Cellular and Molecular Life Sciences. 68 (6): 991–1003. S2CID 31720000.