ArticleThe EMBO journal2003
Upstream AUGs in embryonic proinsulin mRNA control its low translation level.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Cell type-specific expression and subcellular localization of the human insulin upstream open reading frame (INSU) protein in pancreatic β-cells.The Journal of biological chemistry · 2026Article
- A-to-I RNA editing remodels 5'-UTR initiation codons to tune translational output.Scientific reports · 2026Article
- Article
- The Prohormone Proinsulin as a Neuroprotective Factor: Past History and Future Prospects.Frontiers in molecular neuroscience · 2018Review
- Lower Plasma Ghrelin Levels are Found in Women with Diabetes-Complicated Pregnancies.Journal of clinical research in pediatric endocrinology · 2016Article
- Decoding sORF translation - from small proteins to gene regulation.RNA biology · 2016Review
- Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling.eLife · 2016Article
- Upstream AUGs and upstream ORFs can regulate the downstream ORF in Plasmodium falciparum.Malaria journal · 2015Article
- Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.Human gene therapy · 2012Article
- Selected imprinting of INS in the marsupial.Epigenetics & chromatin · 2012Article
- Focus on molecules: proinsulin in the eye: precursor or pioneer?Experimental eye research · 2012Article
- Alternative Mechanisms to Initiate Translation in Eukaryotic mRNAs.Comparative and functional genomics · 2012Article
- Glucose-stimulated translation regulation of insulin by the 5' UTR-binding proteins.The Journal of biological chemistry · 2011Article
- Proinsulin: from hormonal precursor to neuroprotective factor.Frontiers in molecular neuroscience · 2011Article
- Allele-specific recognition of the 3' splice site of INS intron 1.Human genetics · 2010Article
- Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5'-untranslated region.The Journal of biological chemistry · 2010Article
- The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue.BMC research notes · 2009Article
- Proinsulin in development: New roles for an ancient prohormone.Diabetologia · 2006Review
- The regulated expression of chimeric tyrosine hydroxylase-insulin transcripts during early development.Nucleic acids research · 2006Article
- Developmental regulation of a proinsulin messenger RNA generated by intron retention.EMBO reports · 2005Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proinsulin is expressed prior to development of the pancreas and promotes cell survival. Here we study the mechanism affecting the translation efficiency of a specific embryonic proinsulin mRNA. This transcript shares the coding region with the pancreatic form, but presents a 32 nt extended leader region. Translation of proinsulin is markedly reduced by the presence of two upstream AUGs within the 5' extension of the embryonic mRNA. This attenuation is lost when the two upstream AUGs are mutated to AAG, leading to translational efficiency similar to that of the pancreatic mRNA. The upstream AUGs are recognized as initiator codons, because expression of upstream ORF is detectable from the embryonic transcript, but not from the mutated or the pancreatic mRNAs. Strict regulation of proinsulin biosynthesis appears to be necessary, since exogenous proinsulin added to embryos in ovo decreased apoptosis and generated abnormal developmental traits. A novel mechanism for low level proinsulin expression thus relies on upstream AUGs within a specific form of embryonic proinsulin mRNA, emphasizing its importance as a tightly regulated developmental signal.
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