Evidence map›Paper›PMID 30333515›Full record

ArticleScientific reports2018

Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs.

Erin L Sternburg, Jason A Estep, Daniel K Nguyen, Yahui Li, Fedor V Karginov

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

27 citing papers in PubMed, 52 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

5 authors at 1 institution in 1 country.

Erin L SternburgDepartment of Molecular, Cell and Systems Biology, Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA, 92521, USA.
Jason A EstepDepartment of Molecular, Cell and Systems Biology, Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA, 92521, USA.
Daniel K NguyenDepartment of Molecular, Cell and Systems Biology, Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA, 92521, USA.
Yahui LiDepartment of Molecular, Cell and Systems Biology, Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA, 92521, USA.
Fedor V KarginovDepartment of Molecular, Cell and Systems Biology, Institute for Integrative Genome Biology, University of California at Riverside, Riverside, CA, 92521, USA. karginov@ucr.edu.ORCID http://orcid.org/0000-0001-6439-369X
University of California, Riverside · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Approximately 1500 RNA-binding proteins (RBPs) profoundly impact mammalian cellular function by controlling distinct sets of transcripts, often using sequence-specific binding to 3' untranslated regions (UTRs) to regulate mRNA stability and translation. Aside from their individual effects, higher-order combinatorial interactions between RBPs on specific mRNAs have been proposed to underpin the regulatory network. To assess the extent of such co-regulatory control, we took a global experimental approach followed by targeted validation to examine interactions between two well-characterized and highly conserved RBPs, Argonaute2 (AGO2) and Pumilio (PUM1 and PUM2). Transcriptome-wide changes in AGO2-mRNA binding upon PUM knockdown were quantified by CLIP-seq, and the presence of PUM binding on the same 3'UTR corresponded with cooperative and antagonistic effects on AGO2 occupancy. In addition, PUM binding sites that overlap with AGO2 showed differential, weakened binding profiles upon abrogation of AGO2 association, indicative of cooperative interactions. In luciferase reporter validation of candidate 3'UTR sites where AGO2 and PUM colocalized, three sites were identified to host antagonistic interactions, where PUM counteracts miRNA-guided repression. Interestingly, the binding sites for the two proteins are too far for potential antagonism due to steric hindrance, suggesting an alternate mechanism. Our data experimentally confirms the combinatorial regulatory model and indicates that the mostly repressive PUM proteins can change their behavior in a context-dependent manner. Overall, the approach underscores the importance of further elucidation of complex interactions between RBPs and their transcriptome-wide extent.

Indexed as

Gene Expression Regulation3' Untranslated RegionsArgonaute ProteinsBase SequenceBinding SitesGene Expression ProfilingHEK293 CellsHumansRNA-Binding ProteinsRNA InterferenceRNA, MessengerSequence Analysis, DNA3' Untranslated RegionsAGO2 protein, humanArgonaute ProteinsPUM1 protein, humanPUM2 protein, humanRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID30333515
PMCPMC6192998
OpenAlexW2896327811

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LicenceCC BY
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Registered trials

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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.