The Scanning Mechanism of Eukaryotic Translation Initiation
Abstract
In eukaryotes, the translation initiation codon is generally identified by the scanning mechanism, wherein every triplet in the messenger RNA leader is inspected for complementarity to the anticodon of methionyl initiator transfer RNA (Met-tRNA i ). Binding of Met-tRNA i to the small (40S) ribosomal subunit, in a ternary complex (TC) with eIF2-GTP, is stimulated by eukaryotic initiation factor 1 (eIF1), eIF1A, eIF3, and eIF5, and the resulting preinitiation complex (PIC) joins the 5′ end of mRNA preactivated by eIF4F and poly(A)-binding protein. RNA helicases remove secondary structures that impede ribosome attachment and subsequent scanning. Hydrolysis of eIF2-bound GTP is stimulated by eIF5 in the scanning PIC, but completion of the reaction is impeded at non-AUG triplets. Although eIF1 and eIF1A promote scanning, eIF1 and possibly the C-terminal tail of eIF1A must be displaced from the P decoding site to permit base-pairing between Met-tRNA i and the AUG codon, as well as to allow subsequent phosphate release from eIF2-GDP. A second GTPase, eIF5B, catalyzes the joining of the 60S subunit to produce an 80S initiation complex that is competent for elongation.
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The analysis recapitulated the importance of a purine (A or G) at position −3 relative to AUG and a G at +4.
“This analysis recapitulated the importance of a purine (A or G) at position −3 relative to AUG and a G at +4 (Fig. 1e)10,23,24.”
From Human 5′ UTR design and variant effect prediction from a massively parallel translation assay (2019) · cites this paper as [23]
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- Authors
- Hinnebusch, A. G.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hinnebusch, Alan G.
- ORCID
- Hinnebusch, Alan G.
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2014-06-02
- Volume
- 83
- Issue
- 1
- Pages
- 779-812
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2145502099
- Cited by
- 798
- References
- 0
- Citations by year
- 2026: 45 · 2025: 41 · 2024: 68 · 2023: 71 · 2022: 69 · 2021: 67 · 2020: 65 · 2019: 65 · 2018: 82 · 2017: 78 · 2016: 71 · 2015: 61 · 2014: 14
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- translation initiation, scanning mechanism, eukaryotic translation initiation, 40S ribosomal subunit, ternary complex, eIF1, eIF1A, eIF3, eIF5, preinitiation complex, eIF4F, poly(A)-binding protein, RNA helicase, mRNA secondary structure, eIF5B, 80S initiation complex
- MeSH terms
- Animals, Binding Sites, Guanosine Triphosphate, Humans, Hydrolysis, Methionine, Protein Binding, Ribosomes, RNA, Transfer, Met, Tetrahymena, Eukaryotic Initiation Factor-1, Codon, Initiator, Base Pairing, RNA Helicases, Eukaryotic Initiation Factor-3, Eukaryotic Initiation Factor-5, Ribosome Subunits, Small, Eukaryotic
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