Evidence map›Paper›PMID 41361180›Full record

ArticleNature communications2025

A unifying model for microRNA-guided silencing of messenger RNAs.

Tanmay Chatterjee, Shankar Mandal, Sujay Ray, Alexander Johnson-Buck, Nils G Walter

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Exchange dynamics and kinetic control of gene regulation complexes.Nature reviews. Molecular cell biology · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Tanmay ChatterjeeSingle Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Shankar MandalSingle Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Sujay RaySingle Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Alexander Johnson-BuckSingle Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Nils G WalterSingle Molecule Analysis Group and Center for RNA Biomedicine, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA. nwalter@umich.edu.ORCID http://orcid.org/0000-0002-7301-1275

Funding

The RNA nanomachines of the gene expression machinery dissected at the single molecule levelR35GM131922 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NILS G WALTER · 2019 to 2026
$6.9M
Optimization and Validation of Single-Molecule Kinetic Fingerprinting Technology for Rapid, Ultra-Specific Detection of Cancer MutationsR33CA229023 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TEWARI, MUNEESH, WALTER, NILS G · 2018 to 2020
$1.2M
Single-molecule counting of cancer biomarker miRNAs in human biofluidsR21CA204560 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WALTER, NILS G · 2017 to 2019
$614k
NCI NIH HHS R21 CA204560NCI NIH HHS R33 CA229023NIGMS NIH HHS R35 GM131922U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA204560U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA229023U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM131922
6 · The paper itself

Abstract

Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing. Our data suggests conformational rearrangements of the Ago2-bound miRNA that regulate alternative 5'S- and 3'NS-driven target recognition. The resulting model reconciles previously disparate observations and deepens our acumen for successfully marshaling RNA silencing therapies.

Indexed as

MicroRNAsRNA-Induced Silencing ComplexRNA InterferenceRNA, Messenger3' Untranslated RegionsArgonaute ProteinsBase PairingGene SilencingHumansKinetics3' Untranslated RegionsAGO2 protein, humanArgonaute ProteinsMicroRNAsRNA-Induced Silencing ComplexRNA, Messenger

Identifiers

PMID41361180
PMCPMC12804692

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.