Evidence map›Paper›PMID 28939659›Full record

ArticleThe EMBO journal2018

Helix-7 in Argonaute2 shapes the microRNA seed region for rapid target recognition.

Shannon M Klum, Stanley D Chandradoss, Nicole T Schirle, Chirlmin Joo, Ian J MacRae

Abstract read
In one paragraph

Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
–field-weighted citation impact
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

65 citing papers in PubMed.

  1. Article
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  11. The Conundrum of XenomiRs and Human Health.Advances in nutrition (Bethesda, Md.) · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Structural basis for gene silencing by siRNAs in humans.bioRxiv : the preprint server for biology · 2024
    Article
  19. The structural basis for RNA slicing by human Argonaute2.bioRxiv : the preprint server for biology · 2024
    Article
  20. Article

5 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

5 authors.

Shannon M KlumDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Stanley D ChandradossDepartment of BioNanoScience, Kavli Institute of NanoScience, Delft University of Technology, Delft, The Netherlands.
Nicole T SchirleDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Chirlmin JooDepartment of BioNanoScience, Kavli Institute of NanoScience, Delft University of Technology, Delft, The Netherlands c.joo@tudelft.nl macrae@scripps.edu.ORCID 0000-0003-2803-0335
Ian J MacRaeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA c.joo@tudelft.nl macrae@scripps.edu.ORCID 0000-0002-5112-0294

Funding

Structural Basis for RNA Silencing by Human Argonaute2R01GM104475 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI MACRAE, IAN JOHN · 2013 to 2018
$2.2M
Structure and Mechanism of the RISC-loading ComplexR01GM115649 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI MACRAE, IAN JOHN · 2015 to 2018
$1.6M
European Research Council 309509NIGMS NIH HHS R01 GM104475NIGMS NIH HHS R01 GM115649
6 · The paper itself

Abstract

Argonaute proteins use microRNAs (miRNAs) to identify mRNAs targeted for post-transcriptional repression. Biochemical assays have demonstrated that Argonaute functions by modulating the binding properties of its miRNA guide so that pairing to the seed region is exquisitely fast and accurate. However, the mechanisms used by Argonaute to reshape the binding properties of its small RNA guide remain poorly understood. Here, we identify a structural element, α-helix-7, in human Argonaute2 (Ago2) that is required for speed and fidelity in binding target RNAs. Biochemical, structural, and single-molecule data indicate that helix-7 acts as a molecular wedge that pivots to enforce rapid making and breaking of miRNA:target base pairs in the 3' half of the seed region. These activities allow Ago2 to rapidly dismiss off-targets and dynamically search for seed-matched sites at a rate approaching the limit of diffusion.

Indexed as

Models, BiologicalArgonaute ProteinsCrystallography, X-RayHumansMicroRNAsProtein BindingProtein ConformationRNA, Guide, CRISPR-Cas SystemsRNA, MessengerAGO2 protein, humanArgonaute ProteinsMicroRNAsMIRN122 microRNA, humanRNA, Guide, CRISPR-Cas SystemsRNA, MessengerArgonautemicroRNARNA silencingseedtarget search

Identifiers

PMID28939659
PMCPMC5753032

What OpenQuestion holds

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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.