ArticleNucleic acids research2020
eIF2α interactions with mRNA control accurate start codon selection by the translation preinitiation complex.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Substrate Binding Relieves Autoinhibition of the Mammalian GCN2 Kinase.bioRxiv : the preprint server for biology · 2026Article
- Oocyte-specific knockout of eIF2B subunits causes apoptosis of mouse oocytes within the early growing follicles via DNA damage and mitochondrial dysfunction.Cell death & disease · 2026Article
- Translation initiation by the Kozak mRNA sequence is based on a conformational readout on the ribosome.Nature communications · 2026Article
- Oocyte-specific knockout of eIF2 subunits causes apoptosis of mouse oocytes within the early growing follicles via mitochondrial dysfunctions and DNA damage.Cell death & disease · 2026Article
- Distinct uS11/Rps14 interactions with the translation preinitiation complex differentially alter the accuracy of start codon recognition.Nucleic acids research · 2025Article
- Understanding the regulation of protein synthesis under stress conditions.Biophysical journal · 2024Article
- Structural basis of AUC codon discrimination during translation initiation in yeast.Nucleic acids research · 2024Article
- Oocyte-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early-growing follicles by mitochondrial fission defect-reactive oxygen species-DNA damage.Clinical and translational medicine · 2024Article
- The Functional Meaning of 5'UTR in Protein-Coding Genes.International journal of molecular sciences · 2023Review
- Editorial: RNA machines.Frontiers in genetics · 2023Article
- Translation regulatory factor BZW1 regulates preimplantation embryo development and compaction by restricting global non-AUG Initiation.Nature communications · 2022Article
- Molecular architecture of 40S translation initiation complexes on the hepatitis C virus IRES.The EMBO journal · 2022Article
- Functional characterization of 5' UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans.Malaria journal · 2022Article
- Established Protocols for cRNA Expression and Voltage-Clamp Characterization of the P2X7 Receptor in Xenopus laevis Oocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In translation initiation, AUG recognition triggers rearrangement of the 48S preinitiation complex (PIC) from an open conformation to a closed state with more tightly-bound Met-tRNAi. Cryo-EM structures have revealed interactions unique to the closed complex between arginines R55/R57 of eIF2α with mRNA, including the -3 nucleotide of the 'Kozak' context. We found that R55/R57 substitutions reduced recognition of a UUG start codon at HIS4 in Sui- cells (Ssu- phenotype); and in vitro, R55G-R57E accelerated dissociation of the eIF2·GTP·Met-tRNAi ternary complex (TC) from reconstituted PICs with a UUG start codon, indicating destabilization of the closed complex. R55/R57 substitutions also decreased usage of poor-context AUGs in SUI1 and GCN4 mRNAs in vivo. In contrast, eIF2α-R53 interacts with the rRNA backbone only in the open complex, and the R53E substitution enhanced initiation at a UUG codon (Sui- phenotype) and poor-context AUGs, while reducing the rate of TC loading (Gcd- phenotype) in vivo. Consistently, R53E slowed TC binding to the PIC while decreasing TC dissociation at UUG codons in vitro, indicating destabilization of the open complex. Thus, distinct interactions of eIF2α with rRNA or mRNA stabilize first the open, and then closed, conformation of the PIC to influence the accuracy of initiation in vivo.
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