Evidence map›Paper›PMID 30982898›Full record

ArticleNucleic acids research2019

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock.

Violeta Castelo-Szekely, Mara De Matos, Marina Tusup, Steve Pascolo, Jernej Ule, David Gatfield

Abstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Circadian Control of Protein Synthesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Rebirth of the translational machinery: The importance of recycling ribosomes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. A Retrospective on eIF2A-and Not the Alpha Subunit of eIF2.International journal of molecular sciences · 2020
    Review
  19. Crystal structure of the C-terminal domain of DENR.Computational and structural biotechnology journal · 2020
    Article
  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

6 authors.

Violeta Castelo-SzekelyCenter for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
Mara De MatosCenter for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
Marina TusupDepartment of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
Steve PascoloDepartment of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
Jernej UleDepartment of Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
David GatfieldCenter for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The non-canonical initiation factor DENR promotes translation reinitiation on mRNAs harbouring upstream open reading frames (uORFs). Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting involvement of uORF usage and reinitiation in clock regulation. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. We uncovered 240 transcripts with altered translation rate, and used linear regression analysis to extract 5' UTR features predictive of DENR dependence. Among core clock genes, we identified Clock as a DENR target. Using Clock 5' UTR mutants, we mapped the specific uORF through which DENR acts to regulate CLOCK protein biosynthesis. Notably, these experiments revealed an alternative downstream start codon, likely representing the bona fide CLOCK N-terminus. Our findings provide insights into uORF-mediated translational regulation that can regulate the mammalian circadian clock and gene expression at large.

Indexed as

Circadian RhythmOpen Reading Frames5' Untranslated RegionsAnimalsCLOCK ProteinsCloning, MolecularCodon, InitiatorEukaryotic Initiation FactorsFibroblastsGene Expression RegulationHEK293 CellsHumansLuciferasesMiceMutationNIH 3T3 Cells5' Untranslated RegionsClock protein, mouseCLOCK ProteinsCodon, InitiatorDenr protein, mouseEukaryotic Initiation FactorsLuciferasesRNA, Messenger

Identifiers

PMID30982898
PMCPMC6547434

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.