Translation (biology): Difference between revisions

[[File:Protein synthesis.svg|thumb|420x420pxupright=1.65|Overview of the translation of eukaryotic [[messenger RNA]] (mRNA) translation]]

[[ImageFile:Ribosome mRNA translation en.svg|thumb|373x373pxupright=1.5|Diagram showing the translationTranslation of mRNA and theribosomal [[protein synthesis of proteins by a ribosome]]]]

[[File:Translation - Initiation & Elongation.svg|thumb|upright=1.2|Initiation and elongation stages of translation asinvolving seenRNA through zooming in on the nitrogenous bases in RNA[[nucleobase]]s, the ribosome, the[[transfer tRNARNA]], and [[amino acids, with short explanations.acid]]s]]

[[File:Translation drawing- Carina Huerta.svg|thumb|upright=1.3|The three phases of translation: (1) in initiation, polymerasethe small ribosomal subunit binds to the DNARNA strand and moves along until the smallinitiator ribosomaltRNA–amino subunitacid complex binds to the DNA.start Elongationcodon, isculminating initiatedin whenattachment of the large subunit; attaches(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, endwhen a stop codon is reached, a release factor binds and the process[[polypeptide]] ofis elongation.released (note that labels for translocation and peptide bond formation are reversed in this image)]]

In [[molecular biology]] and [[genetics]], '''translation''' is the process in whichliving [[ribosomesCell (biology)|cells]] in thewhich [[cytoplasmprotein]]s orare produced using [[endoplasmic reticulumRNA]] synthesizemolecules proteinsas aftertemplates. theThe processgenerated protein is a sequence of [[transcriptionamino (biology)|transcriptionacid]]s. This sequence is determined by the sequence of [[DNAnucleotides]] toin the [[RNA]]. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the cell'sprotein being generated. The matching from nucleotide triple to amino acid is called the [[nucleusgenetic (cell)|nucleuscode]]. The translation is performed by a large complex of functional RNA and proteins called [[ribosome]]s. The entire process is called [[gene expression]].

In translation, [[mRNA|messenger RNA]] (mRNA)]] is decoded in a ribosome, outside the nucleus, to produce a specific [[amino acid]] chain, or [[polypeptide]]. The polypeptide later [[protein folding|folds]] into an [[Activation energy|active]] [[protein]] and performs its functions in the [[Cell (biology)|cell.]] The [[ribosome]] facilitates decoding by inducing the binding of [[Base pair|complementary]] [[tRNAtransfer 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.

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 [[Eukaryotic small ribosomal subunit (40S)|small ribosomal subunit]] ('''''accommodation''''') transfers the amino acid. itIt carries to the [[Eukaryotic large ribosomal subunit (60S)|large ribosomal subunit]] which binds it to the one of the precedinglypreceding admitted tRNA ('''''transpeptidation'''''). The ribosome then moves to the next mRNA codon to continue the process ('''''translocation'''''), creating an amino acid chain.

In [[prokaryotes]] (bacteria and archaea), translation occurs in the cytosol, where the large and small subunits of the [[ribosome]] bind to the mRNA. In [[eukaryotes]], translation occurs in the [[cytoplasm]] or across the membrane of the [[endoplasmic reticulum]] in a process called [[Protein targeting|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 (biology and chemistry)|vesicle]] transport and [[secretion]] outside the cell, or immediately secreted.

Many types of transcribed RNA, such as transfer RNAtRNA, ribosomal RNA, and small nuclear RNA, do not undergo a translation into proteins.

A number ofSeveral [[antibiotic]]s act by inhibiting translation. These include [[anisomycin]], [[cycloheximide]], [[chloramphenicol]], [[tetracycline]], [[streptomycin]], [[erythromycin]], 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 (biology)|host]]'s cells.

[[Image:Protein translation.gif|thumb|300pxupright=1.1|A ribosome translating a protein that is secreted into the [[endoplasmic reticulum]]. (tRNAs are colored dark blue.)]]

[[Image:TRNA-Phe yeast 1ehz.png|thumb|upright=1.2|Tertiary structure of tRNA. (<span style="color:#E4D00A;">''CCA tail''</span> in yellow, <span style="color:purple;">''Acceptor stem''</span> in purple, <span style="color:orange;">''Variable loop''</span> in orange, <span style="color:red;">''D &nbsp;arm''</span> in red, <span style="color:blue;">''Anticodon arm''</span> in blue with ''Anticodon'' in black, <span style="color:green;">''T &nbsp;arm''</span> in green.|246x246px)]]

The correct amino acid is [[Covalent bond|covalently bonded]] to the correct [[tRNA|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-Dalgarno[[Shine–Dalgarno sequence]]. The Shine-DalgarnoShine–Dalgarno 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-aminotRNA–amino acid complex, [[N-Formylmethionine|f-Met]]-tRNA, to the 30S P site. The initiation phase is completed once a 50S subunit joins the 3030S subunit, forming an active 70S ribosome.<ref name="pmid20467902">{{cite journal | vauthors = Nakamoto T | title = Mechanisms of the initiation of protein synthesis: in reading frame binding of ribosomes to mRNA | journal = Molecular Biology Reports | volume = 38 | issue = 2 | pages = 847–55 | date = February 2011 | pmid = 20467902 | doi = 10.1007/s11033-010-0176-1 | s2cid = 22038744 }}</ref> 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. tRNA usually cannot recognize or bind to stop codons. Instead, the stop codon induces the binding of a [[release factor]] protein<ref>{{cite journal | vauthors = Baggett NE, Zhang Y, Gross CA | title = Global analysis of translation termination in E. coli | journal = PLOS Genetics | volume = 13 | issue = 3 | pages = e1006676 | date = March 2017 | pmid = 28301469 | pmc = 5373646 | doi = 10.1371/journal.pgen.1006676 | veditors = Ibba M | doi-access = free }}</ref> (RF1 & RF2) that prompts the disassembly of the entire ribosome/mRNA complex by the hydrolysis of the polypeptide chain from the peptidyl transferase center <ref name="PTC" /> of the ribosome.<ref>{{cite journal | vauthors = Mora L, Zavialov A, Ehrenberg M, Buckingham RH | title = Stop codon recognition and interactions with peptide release factor RF3 of truncated and chimeric RF1 and RF2 from Escherichia coli | journal = Molecular Microbiology | volume = 50 | issue = 5 | pages = 1467–76 | date = December 2003 | pmid = 14651631 | doi = 10.1046/j.1365-2958.2003.03799.x | doi-access = free }}</ref> 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.<ref name="readthrough">{{cite journal | vauthors = Schueren F, Thoms S | title = Functional Translational Readthrough: A Systems Biology Perspective | journal = PLOS Genetics | volume = 12 | issue = 8 | pages = e1006196 | date = August 2016 | pmid = 27490485 | pmc = 4973966 | doi = 10.1371/JOURNAL.PGEN.1006196 | doi-access = free }}</ref>

[[File:Model M0 of protein synthesis.png|thumb|500 px|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.<ref name= "GH-BMorZin"/>]]

The transcription-translation process description, mentioning only the most basic ”elementary”"elementary" processes, consists of:

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<ref name="pmid5641411">{{cite journal | vauthors = MacDonald CT, Gibbs JH, Pipkin AC | title = Kinetics of biopolymerization on nucleic acid templates | journal = Biopolymers | volume = 6 | issue = 1 | pages = 1–5 | date = 1968 | pmid = 5641411 | doi = 10.1002/bip.1968.360060102 | s2cid = 27559249 }}</ref> 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.<ref>{{cite journal | vauthors = Heinrich R, Rapoport TA | title = Mathematical modelling of translation of mRNA in eucaryotes; steady state, time-dependent processes and application to reticulocytes | journal = Journal of Theoretical Biology | volume = 86 | issue = 2 | pages = 279–313 | date = September 1980 | pmid = 7442295 | doi = 10.1016/0022-5193(80)90008-9 | bibcode = 1980JThBi..86..279H }}</ref><ref name="pmid17031456">{{cite journal | vauthors = Skjøndal-Bar N, Morris DR | title = Dynamic model of the process of protein synthesis in eukaryotic cells | journal = Bulletin of Mathematical Biology | volume = 69 | issue = 1 | pages = 361–93 | date = January 2007 | pmid = 17031456 | doi = 10.1007/s11538-006-9128-2 | s2cid = 83701439 }}</ref> Beyond chemical kinetics, various modeling formalisms such as [[Asymmetric simple exclusion process|Totally Asymmetric Simple Exclusion Process (TASEP)]],<ref name="pmid17031456">{{cite journal | vauthors = Skjøndal-Bar N, Morris DR | title = Dynamic model of the process of protein synthesis in eukaryotic cells | journal = Bulletin of Mathematical Biology | volume = 69 | issue = 1 | pages = 361–93 | date = January 2007 | pmid = 17031456 | doi = 10.1007/s11538-006-9128-2 | s2cid = 83701439 }}</ref> [[Probabilistic logic network|Probabilistic Boolean Networks (PBN)]], [[Petri net|Petri Nets]] and [[Tropical semiring|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,<ref name= "GH-BMorZin">{{cite journal | vauthors = Gorban AN, Harel-Bellan A, Morozova N, Zinovyev A | title = Basic, simple and extendable kinetic model of protein synthesis | journal = Mathematical Biosciences and Engineering | volume = 16 | issue = 6 | pages = 6602–6622 | date = July 2019 | pmid = 31698578 | doi = 10.3934/mbe.2019329 | doi-access = free | arxiv = 1204.5941 }}</ref> following the [[Paradigm#Scientific paradigm|paradigm]] that "useful [[Mathematical model|models]] are simple and extendable".<ref name="pmid28341710">{{cite journal | vauthors = Coyte KZ, Tabuteau H, Gaffney EA, Foster KR, Durham WM | title = Reply to Baveye and Darnault: Useful models are simple and extendable | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 14 | pages = E2804–E2805 | date = April 2017 | pmid = 28341710 | pmc = 5389313 | doi = 10.1073/pnas.1702303114 | bibcode = 2017PNAS..114E2804C | doi-access = free }}</ref> 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.<ref name="pmid22850425">{{cite journal | vauthors = Morozova N, Zinovyev A, Nonne N, Pritchard LL, Gorban AN, Harel-Bellan A | title = Kinetic signatures of microRNA modes of action | journal = RNA | volume = 18 | issue = 9 | pages = 1635–55 | date = September 2012 | pmid = 22850425 | pmc = 3425779 | doi = 10.1261/rna.032284.112 }}</ref> 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.

This will give you the [[primary structure]] of the protein. However, [[protein folding|proteins tend to fold]], depending in part on [[hydrophilic]] and [[hydrophobic]] segments along the chain. [[Secondary structure]] can often still be guessed at, but the proper [[tertiary structure]] is often very hard to determine.

Whereas other aspects such as the 3D structure, called [[tertiary structure]], of protein can only be predicted using [[Protein structure prediction|sophisticated algorithms]], the amino acid sequence, called [[primary structure]], can be determined solely from the nucleic acid sequence with the aid of a [[Codon Dictionary|translation table]].

Example: Condensed translation table for the Standard Genetic Code (from the NCBI Taxonomy webpage).<ref name="NCBI2019">{{Cite web |last1=Elzanowski |first1=Andrzej |last2=Ostell |first2=Jim |date=January 2019 |title=The Genetic Codes |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi |url-status=live |access-date=31 May 2022 |website= |publisher=[[National Center for Biotechnology Information]] (NCBI)}}</ref>

# The [[Condylostoma_nuclear_codeCondylostoma nuclear code|''Condylostoma'' nuclear code]]

# The [[Mesodinium_nuclear_codeMesodinium nuclear code|''Mesodinium'' nuclear code]]

* {{cite journal | vauthors = Malys N, McCarthy JE | title = Translation initiation: variations in the mechanism can be anticipated | journal = Cellular and Molecular Life Sciences | volume = 68 | issue = 6 | pages = 991–1003 | date = March 2011 | pmid = 21076851 | doi = 10.1007/s00018-010-0588-z | s2cid = 31720000 | pmc = 11115079 }}

* [http://vcell.ndsu.nodak.edu/animations/translation/index.htm Virtual Cell Animation Collection: Introducing Translation]

* [http://web.expasy.org/translate Translate tool (from DNA or RNA sequence)]