Translation Initiation: Molecular Mechanisms in Eukaryotes

Abstract

Initiation is the first phase in protein synthesis, during which eukaryotic initiation factors assemble an 80S ribosome at an initiation codon of a messenger RNA (mRNA) such that this triplet is base‐paired to the CAU anticodon of aminoacylated initiator methionyl‐transfer RNA in the ribosomal peptidyl site. Initiation is followed by the elongation phase, in which the 80S ribosome moves along the mRNA, translating the open reading frame into protein.

Keywords: eukaryotic translation initiation factor; messenger ribonucleic acid; ribosome; transfer ribonucleic acid; translation initiation

Figure 1.

Schematic model of the pathway of 48S initiation complex formation on a capped eukaryotic messenger ribonucleic acid (mRNA). Dissociation of the 80S ribosome into 40S and 60S subunits is effected by eukaryotic translation initiation factor‐1A (eIF1A) and ‐3 (eIF3; step 1). Aminoacylated initiator methionyl‐transfer RNA Met‐t RNAMeti, guanosine triphosphate (GTP) and eIF2 form a ternary complex (step 2) that binds with eIF1A and eIF3 to a 40S subunit to form a 43S preinitiation complex (step 3). eIF4F and associated cofactors cooperate in adenosine triphosphate (ATP)‐dependent binding of the 43S complex to mRNA by creating an unstructured cap‐proximal ribosomal binding site (step 4). The interaction of the eIF4G subunit of cap‐bound eIF4F with the eIF3 component of the 43S complex (indicated by a dashed, double‐headed arrow) promotes attachment of the 43S complex to mRNA. The bound 43S complex requires eIF1 to scan downstream on the 5′ untranslated region (UTR) until it recognizes the initiation codon (step 5). The anticodon of Met‐t RNAMeti is base‐paired to the initiation codon in the resulting 48S complex.

Figure 2.

Schematic model of the pathway of 80S complex formation. Hydrolysis of eIF2‐bound GTP in the 48S complex is triggered by eIF5, possibly leading to release of eIF2–guanosine diphosphate (GDP; step 6). The stage at which eIF1, eIF1A and eIF3 are released is not known. eIF5B–GTP mediates joining of the resulting complex to a 60S ribosomal subunit (step 7). Ribosome‐activated hydrolysis of eIF5B‐bound GTP leads to release of eIF5B–GDP to form an 80S ribosome that is competent to begin protein synthesis (step 8). Inactive eIF2–GDP is recycled by eIF2B to eIF2–GTP, which is again competent to bind Met‐t RNAMeti (step 9).

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References

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Further Reading

Asano K, Clayton J, Shalev A and Hinnebusch AG (2000) A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. Genes and Development 14: 2534–2546.

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Spahn CMT, Beckmann R, Eswar N, et al. (2001) Structure of the 80S ribosome from Saccharomyces cerevisiae – tRNA–ribosome and subunit–subunit interactions. Cell 107: 373–386.

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Hellen, Christopher UT, and Pestova, Tatyana V(Sep 2006) Translation Initiation: Molecular Mechanisms in Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005994]