Evidence map›Paper›PMID 31858614›Full record

ArticleThe EMBO journal2020

Molecular mechanism of translational stalling by inhibitory codon combinations and poly(A) tracts.

Petr Tesina, Laura N Lessen, Robert Buschauer, Jingdong Cheng, Colin Chih-Chien Wu, Otto Berninghausen, Allen R Buskirk, Thomas Becker, Roland Beckmann, Rachel Green

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

122 citing papers in PubMed, 177 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Collided ribosomes are rescued by the endonuclease Rae1 andbioRxiv : the preprint server for biology · 2026
    Article
  5. eIF5A and polyamines restrict mRNA levels in response to ribosome stalls.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026
    Review
  15. Article
  16. Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. Review

62 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 2 countries.

Petr TesinaGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.ORCID 0000-0002-5227-1799
Laura N LessenProgram in Molecular Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-6155-3627
Robert BuschauerGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.
Jingdong ChengGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.
Colin Chih-Chien WuDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Otto BerninghausenGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.
Allen R BuskirkDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas BeckerGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.ORCID 0000-0001-8458-2738
Roland BeckmannGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.ORCID 0000-0003-4291-3898
Rachel GreenDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-9337-2003
Center for Integrated Protein Science Munich · DEHoward Hughes Medical Institute · USJohns Hopkins University · US

Funding

PROGRAM IN MOLECULAR BIOPHYSICST32GM008403 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BARRICK, DOUGLAS E. · 1990 to 2019
$13.5M
Molecular mechanisms of ribosome pausing and the cellular responseR37GM059425 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 2014 to 2023
$3.5M
The Mechanism of Pausing and Restarting Translation in BacteriaR01GM110113 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BUSKIRK, ALLEN ROWDON · 2014 to 2017
$1.2M
Boehringer Ingelheim Fonds (BIF)Deutsche Forschungsgemeinschaft (DFG) BE1814/15-1Howard Hughes Medical Institute (HHMI)NIGMS NIH HHS R01 GM110113NIGMS NIH HHS R37 GM059425NIGMS NIH HHS T32 GM008403
6 · The paper itself

Abstract

Inhibitory codon pairs and poly(A) tracts within the translated mRNA cause ribosome stalling and reduce protein output. The molecular mechanisms that drive these stalling events, however, are still unknown. Here, we use a combination of in vitro biochemistry, ribosome profiling, and cryo-EM to define molecular mechanisms that lead to these ribosome stalls. First, we use an in vitro reconstituted yeast translation system to demonstrate that inhibitory codon pairs slow elongation rates which are partially rescued by increased tRNA concentration or by an artificial tRNA not dependent on wobble base-pairing. Ribosome profiling data extend these observations by revealing that paused ribosomes with empty A sites are enriched on these sequences. Cryo-EM structures of stalled ribosomes provide a structural explanation for the observed effects by showing decoding-incompatible conformations of mRNA in the A sites of all studied stall- and collision-inducing sequences. Interestingly, in the case of poly(A) tracts, the inhibitory conformation of the mRNA in the A site involves a nucleotide stacking array. Together, these data demonstrate a novel mRNA-induced mechanisms of translational stalling in eukaryotic ribosomes.

Indexed as

Protein BiosynthesisCodonCryoelectron MicroscopyModels, MolecularNucleic Acid ConformationPoly ARibosomesRNA, MessengerRNA, TransferSaccharomyces cerevisiaeCodonPoly ARNA, MessengerRNA, Transferdisomeframeshiftribosome collisionstallingtranslation

Identifiers

PMID31858614
PMCPMC6996574
OpenAlexW2995107466

What OpenQuestion holds

Textmetadata
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.