Evidence map›Paper›PMID 25549299›Full record

ArticleeLife2014

Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1.

Eelco van Anken, David Pincus, Scott Coyle, Tomás Aragón, Christof Osman, Federica Lari, Silvia Gómez Puerta, Alexei V Korennykh, Peter Walter

Open access · goldAbstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Functional Characterization ofInternational journal of molecular sciences · 2026
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  14. DoesMicroorganisms · 2021
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  16. Quantitative microscopy reveals dynamics and fate of clustered IRE1α.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  17. Transcriptomic Analysis ofFrontiers in microbiology · 2020
    Article
  18. Clustering of IRE1α depends on sensing ER stress but not on its RNase activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  19. Translation Control ofInternational journal of molecular sciences · 2019
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Eelco van AnkenDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
David PincusDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Scott CoyleDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Tomás AragónDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Christof OsmanDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Federica LariDivision of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Silvia Gómez PuertaDepartment of Gene Therapy and Gene Regulation, Center for Applied Medical Research, Pamplona, Spain.
Alexei V KorennykhDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Peter WalterDepartment of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
University of California, San Francisco · USHoward Hughes Medical Institute · US

Funding

Quantitative approaches to reveal the homeostatic control mechanisms of stress reDP5OD017941 · OD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI PINCUS, DAVID · 2013 to 2017
$2.4M
Howard Hughes Medical Institute
6 · The paper itself

Abstract

Insufficient protein-folding capacity in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). In the ER lumen, accumulation of unfolded proteins activates the transmembrane ER-stress sensor Ire1 and drives its oligomerization. In the cytosol, Ire1 recruits HAC1 mRNA, mediating its non-conventional splicing. The spliced mRNA is translated into Hac1, the key transcription activator of UPR target genes that mitigate ER-stress. In this study, we report that oligomeric assembly of the ER-lumenal domain is sufficient to drive Ire1 clustering. Clustering facilitates Ire1's cytosolic oligomeric assembly and HAC1 mRNA docking onto a positively charged motif in Ire1's cytosolic linker domain that tethers the kinase/RNase to the transmembrane domain. By the use of a synthetic bypass, we demonstrate that mRNA docking per se is a pre-requisite for initiating Ire1's RNase activity and, hence, splicing. We posit that such step-wise engagement between Ire1 and its mRNA substrate contributes to selectivity and efficiency in UPR signaling.

Indexed as

Endoplasmic Reticulum StressSignal TransductionAmino Acid MotifsAmino Acid SequenceArginineBasic-Leucine Zipper Transcription FactorsCluster AnalysisConserved SequenceCytosolMembrane GlycoproteinsModels, BiologicalMolecular Sequence DataProtein MultimerizationProtein Serine-Threonine KinasesProtein Structure, TertiaryRepressor ProteinsArginineBasic-Leucine Zipper Transcription FactorsHAC1 protein, S cerevisiaeIRE1 protein, S cerevisiaeMembrane GlycoproteinsProtein Serine-Threonine KinasesRepressor ProteinsSaccharomyces cerevisiae Proteinsbiochemistrycell biologyendoplasmic reticulummRNA processingmRNA targetingS. cerevisiaestress signalingunfolded protein response

Identifiers

PMID25549299
PMCPMC4279078
OpenAlexW2126889815

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.