Translation Initiation Models in Prokaryotes and Eukaryotes

Translation is one stage of protein synthesis in which messenger ribonucleic acid (mRNA) acts as a template for the synthesis of a polypeptide chain; it consists of four phases: initiation, elongation, termination and ribosome recycling. Initiation of protein synthesis, entailing ribosomal recognition of the mRNA start codon and the setting of the correct reading frame, is the rate‐limiting step of translation and the main target of translation regulation in all cells. However, the mechanism and molecular machinery for initiation have diverged in the primary domains of life: the Bacteria, the Archaea and the Eukarya (eukaryotes). In bacteria, translation initiation is relatively simple, whereas in eukaryotes, it is complex and requires more components. In archaea, despite their prokaryotic phenotype, the machinery for protein synthesis initiation is much more elaborated than in bacteria and presents intriguing similarities with the corresponding eukaryotic process. The features of translational initiation in archaea, bacteria and eukaryotes are reviewed, highlighting the divergent and common aspects of this important cellular process in the three domains of life.

Key Concepts

  • Initiation is the first of four steps of the translation cycle. During initiation, the small ribosomal subunit interacts with the messenger ribonucleic acid (mRNA) and finds the right start codon, thereby setting the correct reading frame for decoding.
  • In all cells, translation initiation is assisted and modulated by several proteins called translation initiation factors (IFs). The most important roles of the IFs are to select the proper initiator transfer RNA, adjust it correctly in the ribosomal P site, ensure the accurate selection of the start codon and prevent the premature joining of the large ribosomal subunit to the pre‐initiation complex.
  • Initiation is the rate‐limiting step of translation. It is the efficiency whereby an mRNA is decoded and the amount of final product is largely determined at the initiation level.
  • In all cells, the principal mechanisms of translational control act at the level of initiation, usually targeting certain IFs that play essential roles in the initiation process.
  • The initiation step of translation has incurred a marked evolutionary divergence. The mechanism and components of initiation differ in several aspects in the three primary domains of life, that is, the Bacteria, the Archaea and the Eukaryotes.
  • The Bacteria have the simplest machinery for translation initiation. However, this is not because they are prokaryotes. The other prokaryotic domain, the Archaea, has a fairly complex machinery for initiation, resembling that of eukaryotes, which have the most complex initiation process.

Keywords: translation; initiation; mRNA ; ribosome; RNA structure

Figure 1. The pre‐initiation complex in bacteria, including the 30S subunit, the three initiation factors and fMet‐tRNAfmet. The Shine–Dalgarno sequence for ribosome docking is shown in red.
Figure 2. The scanning model for eukaryotic initiation.
Figure 3. Secondary structure in the 5′‐UTR of an mRNA hinders ribosome scanning.
close

References

Benelli D and Londei P (2011) Translation initiation in Archaea: conserved and domain‐specific features. Biochemical Society Transactions 39 (1): 89–93.

Doerfel LK and Rodnina MV (2013) Elongation factor P: Function and effects on bacterial fitness. Biopolymers 99 (11): 837–845.

Firth AE and Brierley I (2012) Non‐canonical translation in RNA viruses. Journal of General Virology 93 (Pt 7): 1385–1409.

Grill S , Gualerzi CO , Londei P and Bläsi U (2000) Selective stimulation of translation of leaderless mRNA by IF2: evolutionary implications for translation. EMBO Journal 19: 4101–4110.

Hinnebusch AG (2011) Molecular mechanism of scanning and start codon selection in eukaryotes. Microbiology and Molecular Biology Reviews 75 (3): 434–467.

Hinnebusch AG and Lorsch JR (2014) The mechanism of eukaryotic initiation: new insights and challenges. Cold Spring Harbor Perspectives in Biology 4 (10): pii: a011544. DOI: 10.1101/cshperspect.a011544.

Jackson RJ , Hellen CU and Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nature Reviews Molecular Cell Biology 11 (2): 113–127.

Jackson RJ (2013) The current status of vertebrate cellular mRNA IRESs. Cold Spring Harbor Perspectives in Biology 5 (293(Pt 7):): 1385–1409.

Komar AA , Mazumder B and Merrick WC (2012) A new framework for understanding IRES‐mediated translation. Gene 502 (2): 75–86.

Londei P (2005) Evolution of translation initiation: new insights from the archaea. FEMS Microbiology Reviews 29 (2): 185–200.

Milon P and Rodnina MV (2012) Kinetic control of translation initiation in bacteria. Critical Reviews in Biochemistry and Molecular Biology 47 (4): 334–348.

Simonetti A , Marzi S , Jenner L , et al. (2009) A structural view of translation initiation in bacteria. Cellular and Molecular Life Sciences 66: 423–436.

Wachter A (2014) Gene regulation by structured mRNA elements. Trends Genet. 30 (5): 172–181. DOI: 10.1016/j.tig.2014.03.001.

Further Reading

Deigan KE and Ferré‐D'Amaré AR (2014) Riboswitches: discovery of drugs that target bacterial gene‐regulatory RNAs. Trends in Genetics 30 (5): 172–181.

Geissman T , Marzi S and Romby P (2009) The role of mRNA structure in translational control in bacteria. RNA Biology 6 (2): 153–160.

Gilbert WV (2010) Alternative ways to think about cellular internal ribosome entry. Journal of Biological Chemistry 2010 (285): 29033–29038.

Kong J and Lasko P (2012) Translational control in cellular and developmental processes. Nature Reviews Genetics 13 (6): 383–394.

Loreni F , Mancino M and Biffo S (2014) Translation factors and ribosomal proteins control tumor onset and progression: how? Oncogene 33: 2145–2156.

Voigts‐Hoffman F , Klinge S and Ban N (2012) Structural insights into eukaryoric ribosomes and the initiation of translation. Current Opinion in Structural Biology 22: 768–777.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Londei, Paola(Aug 2015) Translation Initiation Models in Prokaryotes and Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000541.pub3]