Evidence map›Paper›PMID 12446775›Full record

ArticleMolecular and cellular biology2002

Inhibition of translation termination mediated by an interaction of eukaryotic release factor 1 with a nascent peptidyl-tRNA.

Deanna M Janzen, Lyudmila Frolova, Adam P Geballe

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

41 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Translation Termination and Ribosome Recycling in Eukaryotes.Cold Spring Harbor perspectives in biology · 2018
    Review
  10. Roadblocks and resolutions in eukaryotic translation.Nature reviews. Molecular cell biology · 2018
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

3 authors at 2 institutions in 2 countries.

Deanna M JanzenDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Lyudmila Frolova
Adam P Geballe
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

TRANSLATIONAL CONTROL OF CYTOMEGALOVIRUS GENE EXPRESSIONR01AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 1994 to 2017
$6.9M
Translational Control of Cytomegalovirus Gene ExpressionR56AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 2018 to 2018
$440k
Translation termination a chemotherapeutic target?R21CA091329 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 2001 to 2002
$346k
TRANSLATIONAL CONTROL OF CYTOMEGALOVIRUS GENE EXPRESSIONR29AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 1988 to 1992
–
NCI NIH HHS CA91329NIAID NIH HHS AI26672NIAID NIH HHS R01 AI026672
6 · The paper itself

Abstract

Expression of the human cytomegalovirus UL4 gene is inhibited by translation of a 22-codon-upstream open reading frame (uORF2). The peptide product of uORF2 acts in a sequence-dependent manner to inhibit its own translation termination, resulting in persistence of the uORF2 peptidyl-tRNA linkage. Consequently, ribosomes stall at the uORF2 termination codon and obstruct downstream translation. Since termination appears to be the critical step affected by translation of uORF2, we examined the role of eukaryotic release factors 1 and 3 (eRF1 and eRF3) in the inhibitory mechanism. In support of the hypothesis that an interaction between eRF1 and uORF2 contributes to uORF2 inhibitory activity, specific residues in each protein, glycines 183 and 184 of the eRF1 GGQ motif and prolines 21 and 22 of the uORF2 peptide, were found to be necessary for full inhibition of downstream translation. Immunoblot analyses revealed that eRF1, but not eRF3, accumulated in the uORF2-stalled ribosome complex. Finally, increased puromycin sensitivity was observed after depletion of eRF1 from the stalled ribosome complex, consistent with inhibition of peptidyl-tRNA hydrolysis resulting from an eRF1-uORF2 peptidyl-tRNA interaction. These results reveal the paradoxical potential for interactions between a nascent peptide and eRF1 to obstruct the translation termination cascade.

Indexed as

Open Reading FramesProtein BiosynthesisAmino Acid SequenceCell-Free SystemCytomegalovirusHumansMacromolecular SubstancesPeptide Termination FactorsProtein Synthesis InhibitorsPuromycinRibosomesRNA, Transfer, Amino AcylViral ProteinsETF1 protein, humanMacromolecular Substancespeptide-chain-release factor 3Peptide Termination FactorsProtein Synthesis InhibitorsPuromycinRNA, Transfer, Amino AcyltRNA, peptidyl-Viral Proteins

Identifiers

PMID12446775
PMCPMC139875
OpenAlexW2128377981

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.