Evidence map›Paper›PMID 18447585›Full record

ArticlePLoS biology2008

A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay.

Guramrit Singh, Indrani Rebbapragada, Jens Lykke-Andersen

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
216citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% 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

216 citing papers in PubMed, 1 synthesis or guideline pooled it, 336 citations in OpenAlex.

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156 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

3 authors at 1 institution in 1 country.

Guramrit SinghMolecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado, United States of America.
Indrani Rebbapragada
Jens Lykke-Andersen
University of Colorado Boulder · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The nonsense-mediated decay (NMD) pathway subjects mRNAs with premature termination codons (PTCs) to rapid decay. The conserved Upf1-3 complex interacts with the eukaryotic translation release factors, eRF3 and eRF1, and triggers NMD when translation termination takes place at a PTC. Contrasting models postulate central roles in PTC-recognition for the exon junction complex in mammals versus the cytoplasmic poly(A)-binding protein (PABP) in other eukaryotes. Here we present evidence for a unified model for NMD, in which PTC recognition in human cells is mediated by a competition between 3' UTR-associated factors that stimulate or antagonize recruitment of the Upf complex to the terminating ribosome. We identify cytoplasmic PABP as a human NMD antagonizing factor, which inhibits the interaction between eRF3 and Upf1 in vitro and prevents NMD in cells when positioned in proximity to the termination codon. Surprisingly, only when an extended 3' UTR places cytoplasmic PABP distally to the termination codon does a downstream exon junction complex enhance NMD, likely through increasing the affinity of Upf proteins for the 3' UTR. Interestingly, while an artificial 3' UTR of >420 nucleotides triggers NMD, a large subset of human mRNAs contain longer 3' UTRs but evade NMD. We speculate that these have evolved to concentrate NMD-inhibiting factors, such as PABP, in spatial proximity of the termination codon.

Indexed as

RNA Stability3' Untranslated RegionsCells, CulturedCodon, NonsenseCytoplasmEukaryotic Initiation Factor-4AHumansPeptide Termination FactorsPoly APoly(A)-Binding Protein IRNA HelicasesRNA, MessengerTrans-Activators3' Untranslated RegionsCodon, NonsenseETF1 protein, humanEukaryotic Initiation Factor-4APeptide Termination FactorsPoly APoly(A)-Binding Protein IRNA HelicasesRNA, MessengerTrans-ActivatorsUPF1 protein, human

Identifiers

PMID18447585
PMCPMC2689706
OpenAlexW2100785765

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.