Evidence map›Paper›PMID 27511142›Full record

ArticleNature communications2016

Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay.

Sébastien Durand, Tobias M Franks, Jens Lykke-Andersen

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

60 citing papers in PubMed, 93 citations in OpenAlex.

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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.

Sébastien DurandDivision of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Tobias M FranksDivision of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Jens Lykke-AndersenDivision of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
University of California, San Diego · US

Funding

Mechanisms of human RNA turnover and quality controlR35GM118069 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LYKKE-ANDERSEN, JENS · 2016 to 2025
$5.1M
Mechanisms of mRNP remodeling in mRNA turnoverR01GM099717 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LYKKE-ANDERSEN, JENS · 2012 to 2015
$1.2M
NIGMS NIH HHS R01 GM099717NIGMS NIH HHS R35 GM118069
6 · The paper itself

Abstract

Many gene expression factors contain repetitive phosphorylation sites for single kinases, but the functional significance is poorly understood. Here we present evidence for hyperphosphorylation as a mechanism allowing UPF1, the central factor in nonsense-mediated decay (NMD), to increasingly attract downstream machinery with time of residence on target mRNAs. Indeed, slowing NMD by inhibiting late-acting factors triggers UPF1 hyperphosphorylation, which in turn enhances affinity for factors linking UPF1 to decay machinery. Mutational analyses reveal multiple phosphorylation sites contributing to different extents to UPF1 activity with no single site being essential. Moreover, the ability of UPF1 to undergo hyperphosphorylation becomes increasingly important for NMD when downstream factors are depleted. This hyperphosphorylation-dependent feedback mechanism may serve as a molecular clock ensuring timely degradation of target mRNAs while preventing degradation of non-targets, which, given the prevalence of repetitive phosphorylation among central gene regulatory factors, may represent an important general principle in gene expression.

Indexed as

Nonsense Mediated mRNA DecayAdenosine TriphosphateAnimalsBinding SitesDNA Mutational AnalysisElectrophoresis, Gel, Two-DimensionalHeLa CellsHumansMiceNIH 3T3 CellsPhosphorylationRAW 264.7 CellsRNA HelicasesRNA, MessengerTrans-ActivatorsAdenosine TriphosphateRent1 protein, mouseRNA HelicasesRNA, MessengerTrans-ActivatorsUPF1 protein, human

Identifiers

PMID27511142
PMCPMC4987530
OpenAlexW2511288970

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.