Evidence map›Paper›PMID 15037778›Full record

ArticleRNA (New York, N.Y.)2004

Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae.

Kim M Keeling, Jessica Lanier, Ming Du, Joe Salas-Marco, Lin Gao, Anisa Kaenjak-Angeletti, David M Bedwell

Abstract read
In one paragraph

Article in RNA (New York, N.Y.), 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing 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

117 citing papers in PubMed.

  1. Article
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  5. Article
  6. Review
  7. Article
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  10. Article
  11. Article
  12. Article
  13. tRNA therapeutics for genetic diseases.Nature reviews. Drug discovery · 2024
    Review
  14. Article
  15. Article
  16. Article
  17. Novel read through agent: ZKN-0013 demonstrates efficacy in APCJournal of molecular medicine (Berlin, Germany) · 2023
    Article
  18. Review
  19. 2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. Article

57 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

7 authors.

Kim M KeelingDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Jessica Lanier
Ming Du
Joe Salas-Marco
Lin Gao
Anisa Kaenjak-Angeletti
David M Bedwell

Funding

TRAINING IN CELLULAR PHYSIOLOGY MEMBRANE TRANSPORTT32DK007545 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUTIERREZ, ORLANDO M · 1987 to 2023
$4.5M
Mechanism of Eukaryotic Translation TerminationR01GM068854 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BEDWELL, DAVID M. · 2003 to 2011
$2.5M
BASIC MECHANISMS OF LUNG DISEASEST32HL007553 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YOTHER, JANET L · 1985 to 2007
$2.2M
BASIC MECHANISMS IN VIROLOGYT32AI007150 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PREVELIGE, PETER E. · 1985 to 2007
$1.7M
NHLBI NIH HHS T32 HL007553NHLBI NIH HHS T32 HL07553NIAID NIH HHS T32 AI007150NIAID NIH HHS T32 AI07150NIDDK NIH HHS T32 DK007545NIDDK NIH HHS T32 DK07545NIGMS NIH HHS R01 GM 068854NIGMS NIH HHS R01 GM068854
6 · The paper itself

Abstract

The Nonsense-Mediated mRNA Decay (NMD) pathway mediates the rapid degradation of mRNAs that contain premature stop mutations in eukaryotic organisms. It was recently shown that mutations in three yeast genes that encode proteins involved in the NMD process, UPF1, UPF2, and UPF3, also reduce the efficiency of translation termination. In the current study, we compared the efficiency of translation termination in a upf1Delta strain and a [PSI(+)] strain using a collection of translation termination reporter constructs. The [PSI(+)] state is caused by a prion form of the polypeptide chain release factor eRF3 that limits its availability to participate in translation termination. In contrast, the mechanism by which Upf1p influences translation termination is poorly understood. The efficiency of translation termination is primarily determined by a tetranucleotide termination signal consisting of the stop codon and the first nucleotide immediately 3' of the stop codon. We found that the upf1Delta mutation, like the [PSI(+)] state, decreases the efficiency of translation termination over a broad range of tetranucleotide termination signals in a unique, context-dependent manner. These results suggest that Upf1p may associate with the termination complex prior to polypeptide chain release. We also found that the increase in readthrough observed in a [PSI(+)]/upf1Delta strain was larger than the readthrough observed in strains carrying either defect alone, indicating that the upf1Delta mutation and the [PSI(+)] state influence the termination process in distinct ways. Finally, our analysis revealed that the mRNA destabilization associated with NMD could be separated into two distinct forms that correlated with the extent the premature stop codon was suppressed. The minor component of NMD was a 25% decrease in mRNA levels observed when readthrough was >/=0.5%, while the major component was represented by a larger decrease in mRNA abundance that was observed only when readthrough was </=0.5%. This low threshold for the onset of the major component of NMD indicates that mRNA surveillance is an ongoing process that occurs throughout the lifetime of an mRNA.

Indexed as

Codon, NonsenseGenes, ReporterMutationPeptide Chain Termination, TranslationalPeptide Termination FactorsPrionsRNA HelicasesRNA, MessengerSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTrans-ActivatorsCodon, NonsenseNAM7 protein, S cerevisiaePeptide Termination FactorsPrionsRNA HelicasesRNA, MessengerSaccharomyces cerevisiae ProteinsSUP35 protein, S cerevisiaeTrans-Activators

Identifiers

PMID15037778
PMCPMC1262634

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.