ArticleThe Journal of biological chemistry2015
Evidence That Base-pairing Interaction between Intron and mRNA Leader Sequences Inhibits Initiation of HAC1 mRNA Translation in Yeast.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Fundamental and Applicative Aspects of the Unfolded Protein Response in Yeasts.Journal of fungi (Basel, Switzerland) · 2023Review
- Pull-down of Biotinylated RNA and Associated Proteins.Bio-protocol · 2022Article
- Detection of HAC1 mRNA Splicing by RT-PCR in Saccharomyces cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Vps34 and TOR Kinases CoordinateMolecular and cellular biology · 2021Article
- Phosphorylation of Pal2 by the protein kinases Kin1 and Kin2 modulatesScience signaling · 2021Article
- DoesMicroorganisms · 2021Article
- First Come, First Served: Sui Generis Features of the First Intron.Plants (Basel, Switzerland) · 2020Review
- Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress.The Journal of cell biology · 2020Article
- Ribosome depurination by ricin leads to inhibition of endoplasmic reticulum stress-inducedThe Journal of biological chemistry · 2019Article
- tRNA ligase structure reveals kinetic competition between non-conventional mRNA splicing and mRNA decay.eLife · 2019Article
- Translation Control ofInternational journal of molecular sciences · 2019Review
- Central dogma rates and the trade-off between precision and economy in gene expression.Nature communications · 2019Article
- Adaptation to Endoplasmic Reticulum Stress Requires Transphosphorylation within the Activation Loop of Protein Kinases Kin1 and Kin2, Orthologs of Human Microtubule Affinity-Regulating Kinase.Molecular and cellular biology · 2018Article
- Global Proteome Remodeling during ER Stress Involves Hac1-Driven Expression of Long Undecoded Transcript Isoforms.Developmental cell · 2018Article
- Article
- Divergence and Conservation of the Major UPR Branch IRE1-bZIP Signaling Pathway across Eukaryotes.Scientific reports · 2016Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The Hac1 transcription factor in yeast up-regulates a collection of genes that control protein homeostasis. Base-pairing interactions between sequences in the intron and the 5'-untranslated region (5' UTR) of the HAC1 mRNA represses Hac1 protein production under basal conditions, whereas cytoplasmic splicing of the intron by the Ire1 kinase-endonuclease, activated under endoplasmic reticulum stress conditions, relieves the inhibition and enables Hac1 synthesis. Using a random mutational screen as well as site-directed mutagenesis, we identify point mutations within the 5' UTR-intron interaction site that derepress translation of the unspliced HAC1 mRNA. We also show that insertion of an in-frame AUG start codon upstream of the interaction site releases the translational block, demonstrating that an elongating ribosome can disrupt the interaction. Moreover, overexpression of translation initiation factor eIF4A, a helicase, enhances production of Hac1 from an mRNA containing an upstream AUG start codon at the beginning of the base-paired region. These results suggest that the major block of translation occurs at the initiation stage. Supporting this interpretation, the point mutations that enhanced Hac1 production resulted in an increased percentage of the HAC1 mRNA associating with polysomes versus free ribosomal subunits. Thus, our results provide evidence that the 5' UTR-intron interaction represses translation initiation on the unspliced HAC1 mRNA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.