Evidence map›Paper›PMID 26744780›Full record

ArticleeLife2016

Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha.

Janine Weber, Han Bao, Christoph Hartlmüller, Zhiqin Wang, Almut Windhager, Robert Janowski, Tobias Madl, Peng Jin, Dierk Niessing

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  8. InheritedNeurology. Genetics · 2024
    Article
  9. Genes · 2024
    Review
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  17. Neurology. Genetics · 2021
    Article
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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

9 authors at 3 institutions in 3 countries.

Janine WeberInstitute of Structural Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Han BaoDepartment of Human Genetics, Emory University, Atlanta, United States.
Christoph HartlmüllerCenter for Integrated Protein Science Munich, Department of Chemistry, Technische Universität München, Munich, Germany.
Zhiqin WangDepartment of Human Genetics, Emory University, Atlanta, United States.
Almut WindhagerInstitute of Structural Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Robert JanowskiInstitute of Structural Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Tobias MadlInstitute of Structural Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Peng JinDepartment of Human Genetics, Emory University, Atlanta, United States.
Dierk NiessingInstitute of Structural Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-5589-369X
Helmholtz Zentrum München · DEEmory University · USCenter for Integrated Protein Science Munich · DE

Funding

Molecular Basis of rCGG-Mediated NeurodegenerationR01NS051630 · NINDS · EMORY UNIVERSITY · PI NELSON, DAVID LOREN · 2006 to 2023
$9.8M
NINDS NIH HHS R01 NS051630
6 · The paper itself

Abstract

The neuronal DNA-/RNA-binding protein Pur-alpha is a transcription regulator and core factor for mRNA localization. Pur-alpha-deficient mice die after birth with pleiotropic neuronal defects. Here, we report the crystal structure of the DNA-/RNA-binding domain of Pur-alpha in complex with ssDNA. It reveals base-specific recognition and offers a molecular explanation for the effect of point mutations in the 5q31.3 microdeletion syndrome. Consistent with the crystal structure, biochemical and NMR data indicate that Pur-alpha binds DNA and RNA in the same way, suggesting binding modes for tri- and hexanucleotide-repeat RNAs in two neurodegenerative RNAopathies. Additionally, structure-based in vitro experiments resolved the molecular mechanism of Pur-alpha's unwindase activity. Complementing in vivo analyses in Drosophila demonstrated the importance of a highly conserved phenylalanine for Pur-alpha's unwinding and neuroprotective function. By uncovering the molecular mechanisms of nucleic-acid binding, this study contributes to understanding the cellular role of Pur-alpha and its implications in neurodegenerative diseases.

Indexed as

Nucleic Acid ConformationAnimalsCrystallography, X-RayDNA, Single-StrandedDrosophilaDrosophila ProteinsGene DeletionGenetic Complementation TestModels, MolecularProtein BindingProtein ConformationTranscription FactorsDNA, Single-StrandedDrosophila ProteinsPur-alpha protein, DrosophilaTranscription Factors5q31.3 microdeletion syndromeALSbiochemistrybiophysicsDNA-/RNA-protein interactionDNA unwindingFXTAS<i>d. melanogaster</i><i>e. coli</i>structural biologyX-ray crystallography

Identifiers

PMID26744780
PMCPMC4764581
OpenAlexW2224450938

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.