Translation (biology)

Overview of the translation of eukaryotic messenger RNA

Diagram showing the translation of mRNA and the synthesis of proteins by a ribosome

In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or ER synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is called gene expression.

In translation, messenger RNA (mRNA) is decoded in a ribosome to produce a specific amino acid chain, or polypeptide. The polypeptide later folds into an active protein and performs its functions in the cell. The ribosome 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:

1. 
   Initiation: The ribosome assembles around the target mRNA. The first tRNA is attached at the start codon.


2. 
   Elongation: The tRNA transfers an amino acid to the tRNA corresponding to the next codon. The ribosome then moves (translocates) to the next mRNA codon to continue the process, creating an amino acid chain.


3. 
   
   
   

   
   

   The three phases of translation initiation polymerase binds to the DNA strand and moves along until the small ribosomal subunit binds to the DNA. Elongation is initiated when the large subunit attaches and termination end the process of elongation.

   
   
   
   Termination: When a stop codon is reached, the ribosome releases the polypeptide.

In prokaryotes (bacteria), translation occurs in the cytosol^[1], where the medium and small subunits of the ribosome bind to the tRNA. 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 antibiotics act by inhibiting translation. These include clindamycin, 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's cells.

Contents

• 
  1 Basic mechanisms
  


• 
  2 Genetic code
  
  
  
  • 
    2.1 Translation tables
    
  
  
  
  


• 
  3 See also
  


• 
  4 References
  


• 
  5 Further reading
  


• 
  6 External links
  

Basic mechanisms

Further information: Prokaryotic translation and Eukaryotic translation

A ribosome translating a protein that is secreted into the endoplasmic reticulum. tRNAs are 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.

The basic process of translation is the addition of three amino acids at a time to the end of the polypeptide being formed. This process takes place inside the ribosome. A ribosome is made up of two subunits, a small 40S subunit and a large 60S 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.^[2] The choice of amino acid type to be added is determined by the genetic code on the 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 polypeptide.^[3]
Addition of an amino acid occurs at the C-terminus of the peptide and thus translation is said to be amino-to-carboxyl directed.^[4]

The mRNA carries genetic information encoded as a DNA sequence from the chromosomes to the nucleolus. 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.

The ribosome molecules translate this code to a specific sequence of amino acids. The ribosome is a multi-subunit structure containing rRNA and proteins. It is the "factory" where amino acids are assembled into proteins.
tRNAs are small noncoding RNA chains (75-90 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 synthetases (enzymes) catalyze the bonding between specific tRNAs and the amino acids that their anticodon sequences call for. The product of this reaction is an aminoacyl-tRNA. In prokaryotes, this aminoacyl-tRNA is carried to the ribosome by EF-Tu, where mRNA codons are matched through complementary base pairing 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"^[5] 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.^[6]

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 (in prokaryotes) and eEF-2 (in eukaryotes) 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 4n+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).^[7]

Even though the ribosomes are usually considered accurate, 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 and 1/10³ misincorporated amino acids, depending on the experimental conditions.^[8] The rate of premature translation abandonment, instead, has been estimated to be of the order of magnitude of 10⁻⁴ events per translated codon.^[9]
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 prokaryotes, initiation of protein synthesis involves the recognition of a purine-rich initiation sequence on the mRNA called the Shine-Dalgarno sequence. The Shine-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-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.^[10] Termination of the polypeptide happens when the A site of the ribosome faces 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 that prompts the disassembly of the entire ribosome/mRNA complex and the hydrolysis and the release of the polypeptide chain from 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.^[11]

The process of translation is highly regulated in prokaryotic and eukaryotic 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.^[12]

Genetic code

Main article: Genetic code

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 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. 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).

 AAs    = FFLLSSSSYY**CC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG

 Starts = ---M---------------M---------------M----------------------------

 Base1  = TTTTTTTTTTTTTTTTCCCCCCCCCCCCCCCCAAAAAAAAAAAAAAAAGGGGGGGGGGGGGGGG

 Base2  = TTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGGTTTTCCCCAAAAGGGG

 Base3  = TCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAG

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:

1. The Standard


2. The Vertebrate Mitochondrial Code


3. The Yeast Mitochondrial Code


4. The Mold, Protozoan, and Coelenterate Mitochondrial Code and the Mycoplasma/Spiroplasma Code


5. The Invertebrate Mitochondrial Code


6. The Ciliate, Dasycladacean and Hexamita Nuclear Code


7. 
   


9. The Echinoderm and Flatworm Mitochondrial Code


10. The Euplotid Nuclear Code


11. The Bacterial and Plant Plastid Code


12. The Alternative Yeast Nuclear Code


13. The Ascidian Mitochondrial Code


14. The Alternative Flatworm Mitochondrial Code


15. 
    Blepharisma Nuclear Code


16. 
    Chlorophycean Mitochondrial Code


17. 
    


21. Trematode Mitochondrial Code


22. 
    Scenedesmus obliquus mitochondrial Code


23. 
    Thraustochytrium Mitochondrial Code

See also

• DNA codon table


• Expanded genetic code


• Protein methods


• Protein production


• Start codon

References

1. 
   ^ Gualerzi, Claudio O.; Pon, Cynthia L (2002). "Initiation of mRNA translation in prokaryotes". Biochemistry. 29 (25): 5881–5889. doi:10.1021/bi00477a001..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
   


2. 
   ^ Biology. McGraw hill education. 2014. p. 249. ISBN 978-981-4581-85-1.
   


3. 
   ^ Neill C (1996). Biology (Fourth ed.). The Benjamin/Cummings Publishing Company. pp. 309–310. ISBN 978-0-8053-1940-8.
   


4. 
   ^ Stryer L (2002). Biochemistry (Fifth ed.). W. H. Freeman and Company. p. 826. ISBN 978-0-7167-4684-3.
   


5. 
   ^ Moghal A, Mohler K, Ibba M (November 2014). "Mistranslation of the genetic code". FEBS Letters. 588 (23): 4305–10. doi:10.1016/j.febslet.2014.08.035. PMC 4254111. PMID 25220850.
   


6. 
   ^ Griffiths A (2008). "9". Introduction to Genetic Analysis (9th ed.). New York: W.H. Freeman and Company. pp. 335–339. ISBN 978-0-7167-6887-6.
   


7. 
   ^ Ross JF, Orlowski M (February 1982). "Growth-rate-dependent adjustment of ribosome function in chemostat-grown cells of the fungus Mucor racemosus". Journal of Bacteriology. 149 (2): 650–3. PMC 216554. PMID 6799491.
   


8. 
   ^ Wohlgemuth, I; Pohl, C; Mittelstaet, J; Konevega, AL; Rodnina, MV (27 October 2011). "Evolutionary optimization of speed and accuracy of decoding on the ribosome". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366 (1580): 2979–86. doi:10.1098/rstb.2011.0138. PMC 3158919. PMID 21930591.
   


9. 
   ^ Sin, C; Valleriani, A; Chiarugi, D (1 March 2016). "Quantitative assessment of ribosome drop-off in E. coli". Nucleic Acids Research. 44 (6): 2528–37. doi:10.1093/nar/gkw137. PMC 4824120. PMID 26935582.
   


10. 
    ^ Nakamoto, T. (2011). Mechanisms of the initiation of protein synthesis: In reading frame binding of ribosomes to mRNA. Molecular Biology Reports, 38(2), 847-855.
    


11. 
    ^ Schueren F and Thoms S (2016). "Functional Translational Readthrough: A Systems Biology Perspective". PLOS Genetics. 12 (e1006196): 12. doi:10.1371/JOURNAL.PGEN.1006196. PMC 4973966. PMID 27490485.
    


12. 
    ^ Cenik C, Cenik ES, Byeon GW, Grubert F, Candille SI, Spacek D, Alsallakh B, Tilgner H, Araya CL, Tang H, Ricci E, Snyder MP (November 2015). "Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans". Genome Research. 25 (11): 1610–21. doi:10.1101/gr.193342.115. PMC 4617958. PMID 26297486.
    

Further reading

• 
  Champe PC, Harvey RA, Ferrier DR (2004). Lippincott's Illustrated Reviews: Biochemistry (3rd ed.). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-2265-0.
  


• 
  Cox M, Nelson DR, Lehninger AL (2005). Lehninger principles of biochemistry (4th ed.). San Francisco...: W.H. Freeman. ISBN 978-0-7167-4339-2.
  


• 
  Malys N, McCarthy JE (March 2011). "Translation initiation: variations in the mechanism can be anticipated". Cellular and Molecular Life Sciences. 68 (6): 991–1003. doi:10.1007/s00018-010-0588-z. PMID 21076851.
  

External links

Wikimedia Commons has media related to Translation (biology).

• Virtual Cell Animation Collection: Introducing Translation


• Translate tool (from DNA or RNA sequence)

v t e Gene expression
Introduction to genetics	Genetic code Central dogma DNA → RNA → Protein Special transfers RNA→RNA RNA→DNA Protein→Protein
Transcription	Types Bacterial Eukaryotic Key elements Transcription factor RNA polymerase Promoter Post-transcription Precursor mRNA (pre-mRNA / hnRNA) 5' capping Splicing Polyadenylation Histone acetylation and deacetylation
Translation	Types Prokaryotic Eukaryotic Key elements Ribosome Transfer RNA (tRNA) Ribosome-nascent chain complex (RNC) Post-translational modification (functional groups · peptides · structural changes)
Regulation	Epigenetic imprinting Transcriptional Gene regulatory network cis-regulatory element lac operon Post-transcriptional sequestration (P-bodies) alternative splicing microRNA Translational Post-translational reversible irreversible
Influential people	François Jacob Jacques Monod
Portal

v t e Protein biosynthesis: translation (bacterial, archaeal, eukaryotic)
Proteins	Initiation factor Bacterial PIF-1 PIF-2 PIF-3 Archaeal aIF1 aIF2 aIF5 aIF6 Eukaryotic .mw-parser-output .nobold{font-weight:normal} eIF1 eIF1 EIF1AX AY 1B eIF2 EIF2S1 EIF2S2 EIF2S3 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2B5 EIF-2 kinase eIF2A eIF2D eIF3 EIF3A B C D E F G H I J K L M eIF4 EIF4A2 A3 B E1 E2 E3 G1 G2 G3 H eIF5 EIF5 EIF5A A2 5B eIF6 EIF6 Elongation factor Bacterial EF-Tu EF-Ts EF-G Archaeal aEF-1 aEF-2 Eukaryotic EEF-1 EEF1A1 EEF1A2 EEF1A3 EEF1B1 EEF1B2 EEF1B3 EEF1B4 EEF1D EEF1E1 EEF1G EEF2 Release factor Bacterial Archaeal Eukaryotic (ETF1) Ribosomal Proteins Cytoplasmic 60S subunit RPL3 RPL4 RPL5 RPL6 RPL7 RPL7A RPL8 RPL9 RPL10 RPL10A RPL10-like RPL11 RPL12 RPL13 RPL13A RPL14 RPL15 RPL17 RPL18 RPL18A RPL19 RPL21 RPL22 RPL23 RPL23A RPL24 RPL26 RPL27 RPL27A RPL28 RPL29 RPL30 RPL31 RPL32 RPL34 RPL35 RPL35A RPL36 RPL36A RPL37 RPL37A RPL38 RPL39 RPL40 RPL41 RPLP0 RPLP1 RPLP2 RRP15-like RSL24D1 40S subunit RPSA RPS2 RPS3 RPS3A RPS4 (RPS4X, RPS4Y1, RPS4Y2) RPS5 RPS6 RPS7 RPS8 RPS9 RPS10 RPS11 RPS12 RPS13 RPS14 RPS15 RPS15A RPS16 RPS17 RPS18 RPS19 RPS20 RPS21 RPS23 RPS24 RPS25 RPS26 RPS27 RPS27A RPS28 RPS29 RPS30 RACK1 Mitochondrial 39S subunit MRPL1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 28S subunit MRPS1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Other concepts	Aminoacyl tRNA synthetase Reading frame Start codon Stop codon Shine-Dalgarno sequence/Kozak consensus sequence

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