Evidence map›Paper›PMID 20505670›Full record

ArticleNature2010

Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2.

Filipp Frank, Nahum Sonenberg, Bhushan Nagar

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 364 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
364citing papers in PubMed, 1 pooled it
19.2field-weighted citation impact, top 1% 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

364 citing papers in PubMed, 1 synthesis or guideline pooled it, 627 citations in OpenAlex.

  1. Pooled it
  2. In silico unwinding ofRNA biology · 2026
    Article
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  4. Review
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  16. Plant microRNA maturation and function.Nature reviews. Molecular cell biology · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. Review

304 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

3 authors at 1 institution in 1 country.

Filipp FrankDepartment of Biochemistry, McGill University, Montréal, Québec H3G 0B1, Canada.
Nahum Sonenberg
Bhushan Nagar
McGill University · CA

Funding

Canadian Institutes of Health Research MOP-82929
6 · The paper itself

Abstract

MicroRNAs (miRNAs) mediate post-transcriptional gene regulation through association with Argonaute proteins (AGOs). Crystal structures of archaeal and bacterial homologues of AGOs have shown that the MID (middle) domain mediates the interaction with the phosphorylated 5' end of the miRNA guide strand and this interaction is thought to be independent of the identity of the 5' nucleotide in these systems. However, analysis of the known sequences of eukaryotic miRNAs and co-immunoprecipitation experiments indicate that there is a clear bias for U or A at the 5' position. Here we report the crystal structure of a MID domain from a eukaryotic AGO protein, human AGO2. The structure, in complex with nucleoside monophosphates (AMP, CMP, GMP, and UMP) mimicking the 5' end of miRNAs, shows that there are specific contacts made between the base of UMP or AMP and a rigid loop in the MID domain. Notably, the structure of the loop discriminates against CMP and GMP and dissociation constants calculated from NMR titration experiments confirm these results, showing that AMP (0.26 mM) and UMP (0.12 mM) bind with up to 30-fold higher affinity than either CMP (3.6 mM) or GMP (3.3 mM). This study provides structural evidence for nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins and explains the observed preference for U or A at the 5' end of miRNAs.

Indexed as

Adenosine MonophosphateArgonaute ProteinsBase SequenceCrystallography, X-RayCytidine MonophosphateEukaryotic Initiation Factor-2Guanosine MonophosphateHumansKineticsMagnetic Resonance SpectroscopyModels, MolecularProtein Structure, TertiaryRNA, Small UntranslatedStructure-Activity RelationshipSubstrate SpecificityThermodynamicsAdenosine MonophosphateAGO2 protein, humanArgonaute ProteinsCytidine MonophosphateEukaryotic Initiation Factor-2Guanosine MonophosphateRNA, Small UntranslatedUridine Monophosphate

Identifiers

PMID20505670
OpenAlexW2111452477

What OpenQuestion holds

Textmetadata
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.