ArticlePLoS genetics2011
Translation reinitiation relies on the interaction between eIF3a/TIF32 and progressively folded cis-acting mRNA elements preceding short uORFs.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Global translational reprogramming inVirulence · 2026Article
- Elongationless start-stop elements are stress-resilient translation gates that are more repressive than uTranslons.Nucleic acids research · 2026Article
- Research Progress on Heavy Metals as Regulators of Bacterial Virulence in aPathogens (Basel, Switzerland) · 2026Review
- PRRC2A, PRRC2B and PRRC2C are Stress Granule Proteins that Promote Translation Through Association with the eIF3 complex.bioRxiv : the preprint server for biology · 2026Article
- A hidden intrinsic ability of bicistronic expression based on a novel translation reinitiation mechanism in yeast.Nucleic acids research · 2025Article
- Differential effects of 40S ribosome recycling factors on reinitiation at regulatory uORFs in GCN4 mRNA are not dictated by their roles in bulk 40S recycling.Communications biology · 2024Article
- Impacts of yeast Tma20/MCTS1, Tma22/DENR and Tma64/eIF2D on translation reinitiation and ribosome recycling.bioRxiv : the preprint server for biology · 2024Article
- The molecular basis of translation initiation and its regulation in eukaryotes.Nature reviews. Molecular cell biology · 2024Review
- SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.PLoS pathogens · 2024Article
- RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames.Nucleic acids research · 2024Article
- The ribosome quality control factor Asc1 determines the fate of HSP70 mRNA on and off the ribosome.Nucleic acids research · 2023Article
- Principles, mechanisms, and biological implications of translation termination-reinitiation.RNA (New York, N.Y.) · 2023Article
- Translational regulation by uORFs and start codon selection stringency.Genes & development · 2023Review
- Article
- The Helix-Loop-Helix motif of human EIF3A regulates translation of proliferative cellular mRNAs.PloS one · 2023Article
- Phosphorylation of a reinitiation supporting protein, RISP, determines its function in translation reinitiation.Nucleic acids research · 2021Article
- Exploring Evidence of Non-coding RNA Translation With Trips-Viz and GWIPS-Viz Browsers.Frontiers in cell and developmental biology · 2021Article
- eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.Frontiers in molecular biosciences · 2021Article
- Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome.Scientific reports · 2020Article
- Selective Translation Complex Profiling Reveals Staged Initiation and Co-translational Assembly of Initiation Factor Complexes.Molecular cell · 2020Article
3 more citing papers are in PubMed but not listed here.
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6 authors.
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Abstract
Reinitiation is a gene-specific translational control mechanism characterized by the ability of some short upstream uORFs to retain post-termination 40S subunits on mRNA. Its efficiency depends on surrounding cis-acting sequences, uORF elongation rates, various initiation factors, and the intercistronic distance. To unravel effects of cis-acting sequences, we investigated previously unconsidered structural properties of one such a cis-enhancer in the mRNA leader of GCN4 using yeast genetics and biochemistry. This leader contains four uORFs but only uORF1, flanked by two transferrable 5' and 3' cis-acting sequences, and allows efficient reinitiation. Recently we showed that the 5' cis-acting sequences stimulate reinitiation by interacting with the N-terminal domain (NTD) of the eIF3a/TIF32 subunit of the initiation factor eIF3 to stabilize post-termination 40S subunits on uORF1 to resume scanning downstream. Here we identify four discernible reinitiation-promoting elements (RPEs) within the 5' sequences making up the 5' enhancer. Genetic epistasis experiments revealed that two of these RPEs operate in the eIF3a/TIF32-dependent manner. Likewise, two separate regions in the eIF3a/TIF32-NTD were identified that stimulate reinitiation in concert with the 5' enhancer. Computational modeling supported by experimental data suggests that, in order to act, the 5' enhancer must progressively fold into a specific secondary structure while the ribosome scans through it prior uORF1 translation. Finally, we demonstrate that the 5' enhancer's stimulatory activity is strictly dependent on and thus follows the 3' enhancer's activity. These findings allow us to propose for the first time a model of events required for efficient post-termination resumption of scanning. Strikingly, structurally similar RPE was predicted and identified also in the 5' leader of reinitiation-permissive uORF of yeast YAP1. The fact that it likewise operates in the eIF3a/TIF32-dependent manner strongly suggests that at least in yeasts the underlying mechanism of reinitiation on short uORFs is conserved.
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