ArticleNucleic acids research2017
Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.Nucleic acids research · 2026Article
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.bioRxiv : the preprint server for biology · 2026Article
- The eIF5-mimic protein 5MP1: a regulator of translation stringency and a multifaceted oncogene.Journal of biochemistry · 2026Review
- Halofuginone is a Molecular Glue Degrader of Integrin β4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural basis for non-AUG translation regulation by 5MPs.bioRxiv : the preprint server for biology · 2025Article
- Article
- Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2.RNA (New York, N.Y.) · 2025Article
- Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibitors of eIF1A-ribosome interaction unveil uORF-dependent regulation of translation initiation and antitumor and antiviral effects.The EMBO journal · 2025Article
- Exploring the interaction dynamics of eukaryotic translation initiation factor 2.Biochemical Society transactions · 2025Review
- Systematic identification and characterization of high efficiency Cas9 guide RNAs for therapeutic targeting of ADAR.PloS one · 2025Article
- Dual Luciferase Reporter Assay in Schizosaccharomyces pombe.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Evaluation of Eukaryotic mRNA Coding Potential.Methods in molecular biology (Clifton, N.J.) · 2025Article
- LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression.Neurochemical research · 2024Article
- CriticalNAR genomics and bioinformatics · 2024Article
- Loss-of-function cancer-linked mutations in the EIF4G2 non-canonical translation initiation factor.Life science alliance · 2024Article
- BZW2 promotes malignant progression in lung adenocarcinoma through enhancing the ubiquitination and degradation of GSK3β.Cell death discovery · 2024Article
- Start codon-associated ribosomal frameshifting mediates nutrient stress adaptation.Nature structural & molecular biology · 2023Article
- Translational regulation by uORFs and start codon selection stringency.Genes & development · 2023Review
- Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding.Nucleic acids research · 2023Article
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
In the human genome, translation initiation from non-AUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP.
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