Evidence map›Paper›PMID 30418581›Full record

ArticleNucleic acids research2019

HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs.

Marta Pabis, Grzegorz M Popowicz, Ralf Stehle, David Fernández-Ramos, Sam Asami, Lisa Warner, Sofía M García-Mauriño, Andreas Schlundt, María L Martínez-Chantar, Irene Díaz-Moreno and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

61 citing papers in PubMed, 120 citations in OpenAlex.

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1 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

11 authors at 4 institutions in 3 countries.

Marta PabisInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Grzegorz M PopowiczInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Ralf StehleInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
David Fernández-RamosCIC bioGUNE, Centro de Investigación Cooperativa en Biociencias. Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain.
Sam AsamiInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Lisa WarnerInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Sofía M García-MauriñoInstituto de Investigaciones Químicas (IIQ)-Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla - Consejo Superior de Investigaciones Científicas (CSIC), Avda. Americo Vespucio 49, 41092 Sevilla, Spain.
Andreas SchlundtInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
María L Martínez-ChantarCIC bioGUNE, Centro de Investigación Cooperativa en Biociencias. Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain.
Irene Díaz-MorenoInstituto de Investigaciones Químicas (IIQ)-Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla - Consejo Superior de Investigaciones Científicas (CSIC), Avda. Americo Vespucio 49, 41092 Sevilla, Spain.
Michael SattlerInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Center for Integrated Protein Science Munich · DEConsejo Superior de Investigaciones Científicas · ESInstituto de Salud Carlos III · ESJagiellonian University · PL

Funding

Women's health: interplay of maternal diet and key demographics on neurological health in the rural frontier and remote WestP20GM103408 · NIGMS · UNIVERSITY OF IDAHO · PI Scott A Minnich · 2012 to 2026
$59.8M
NIGMS NIH HHS P20 GM103408
6 · The paper itself

Abstract

HuR/ELAVL1 is an RNA-binding protein involved in differentiation and stress response that acts primarily by stabilizing messenger RNA (mRNA) targets. HuR comprises three RNA recognition motifs (RRMs) where the structure and RNA binding of RRM3 and of full-length HuR remain poorly understood. Here, we report crystal structures of RRM3 free and bound to cognate RNAs. Our structural, NMR and biochemical data show that RRM3 mediates canonical RNA interactions and reveal molecular details of a dimerization interface localized on the α-helical face of RRM3. NMR and SAXS analyses indicate that the three RRMs in full-length HuR are flexibly connected in the absence of RNA, while they adopt a more compact arrangement when bound to RNA. Based on these data and crystal structures of tandem RRM1,2-RNA and our RRM3-RNA complexes, we present a structural model of RNA recognition involving all three RRM domains of full-length HuR. Mutational analysis demonstrates that RRM3 dimerization and RNA binding is required for functional activity of full-length HuR in vitro and to regulate target mRNAs levels in human cells, thus providing a fine-tuning for HuR activity in vivo.

Indexed as

Cell Line, TumorELAV-Like Protein 1HumansModels, MolecularNuclear Magnetic Resonance, BiomolecularProtein BindingProtein MultimerizationRNAELAVL1 protein, humanELAV-Like Protein 1RNA

Identifiers

PMID30418581
PMCPMC6344896
OpenAlexW2900307975

What OpenQuestion holds

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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.