Evidence map›Paper›PMID 40671527›Full record

ArticleNucleic acids research2025

Sequence, structure, and affinity of miR-34a binding sites determine repression efficacy.

Lara Sweetapple, David M Kosek, Elnaz Banijamali, Walter Becker, Juliane Müller, Christina Karadiakos, Lorenzo Baronti, Ileana Guzzetti, Dimitri Schritt, Alan Chen and 2 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Systemic Molecular Alterations ofInternational journal of molecular sciences · 2026
    Article
  4. Article
  5. Targeted NMR signal enhancement of RNA by site-directed bis-nitroxide labeling.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
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

12 authors.

Lara SweetappleDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.
David M KosekDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, 171 77 Sweden.ORCID 0000-0002-0192-4761
Elnaz BanijamaliDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.ORCID 0000-0003-4718-9720
Walter BeckerDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.
Juliane MüllerDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.
Christina KaradiakosDepartment of Chemistry, University at Albany, Albany, NY 12222, United States.
Lorenzo BarontiDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.
Ileana GuzzettiDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.
Dimitri SchrittDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, 171 77 Sweden.
Alan ChenDepartment of Chemistry, University at Albany, Albany, NY 12222, United States.ORCID 0000-0001-8246-2935
Emma R AnderssonDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, 171 77 Sweden.ORCID 0000-0002-8608-625X
Katja PetzoldDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden.ORCID 0000-0001-9470-0347

Funding

Thermodynamically Calibrated RNA Simulations to Decode Mechanisms of RNAMolecular RecognitionR35GM133469 · NIGMS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI Alan Austin Chen · 2019 to 2026
$2.9M
Cancerfonden 21 1770 PjKarolinska InstituteKnut and Alice Wallenberg Foundation KAW 2016.0087NIGMS NIH HHS R35 GM133469NIGMS NIH HHS R35GM133469NIH HHSStiftelse för Strategist Forskning SSF FFL15-0178
6 · The paper itself

Abstract

MicroRNAs (miRs) regulate gene expression post-transcriptionally by guiding Argonaute (AGO) proteins to target mRNAs. Efficiently predicting the repressive effects of miRNAs remains limited largely due to an incomplete understanding of how mRNA:miR structure affects function. Using EMSAs, structural probing, luciferase reporter assays, and transcriptome analysis, we investigated the structural, biophysical, and functional interaction between the human tumour suppressor miR-34a and 12 mRNA targets. Comparison of isolated mRNA:miRNA duplexes and those bound within functional AGO2 revealed that while the binary duplex largely predicts AGO2-associated affinity and structure, AGO2 bidirectionally modulates binding by attenuating strong interactions and stabilising weaker ones. Furthermore, we show that the impact of supplementary pairing is more pronounced in targets with shorter seeds compared to those with full-length seeds and confirm this effect in a transcriptome-wide analysis. Finally, we identified three structural groups of mRNA:miR-34a-AGO2 complexes, adopting either a symmetrical structure, or a bulge on the mRNA or miR side. miR-bulged complex repression was strongly linked to mRNA:miR affinity, whereas mRNA-bulged complexes showed no such correlation. Our results thus identify structural and biophysical characteristics of mRNA:miR duplexes that contribute to repression efficacy, revealing a hierarchy of seed type, structure, and affinity that determine repression efficiency.

Indexed as

Argonaute ProteinsMicroRNAsRNA, MessengerBase SequenceBinding SitesHumansNucleic Acid ConformationAGO2 protein, humanArgonaute ProteinsMicroRNAsMIRN34 microRNA, humanRNA, Messenger

Identifiers

PMID40671527
PMCPMC12266142

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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.