ArticleNucleic acids research2023
Efficient 3'-pairing renders microRNA targeting less sensitive to mRNA seed accessibility.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- The AGO2 adaptor LIMD1 expands the functional and evolutionary reach of microRNA targeting.Science advances · 2026Article
- U2 snRNP recognizes the branch site through a loaded-spring strand-invasion mechanism.Nucleic acids research · 2026Article
- The history and function of a circular RNA.Nature communications · 2026Review
- MicroRNA isomiRs reveal novel pathways linked to disease activity and fibrosis in MASLD.Clinical and molecular hepatology · 2026Article
- 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 · 2026Article
- RIMap-RISC: a transcriptome-wide database of structurally modeled human microRNA interactions.Genome biology · 2026Article
- Engineered MSC-Exosomes Delivering miRNAs for Respiratory Disease Diagnostics and Therapy: Opportunities and Challenges.International journal of nanomedicine · 2026Review
- Target-Directed miRNA Degradation: Mechanisms and Significance.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Computational analysis of miRNA mediated KDR gene regulation and natural VEGFR2 inhibitors from Persicaria hydropiper in hepatocellular carcinoma.Scientific reports · 2025Article
- An endogenous cluster of target-directed microRNA degradation sites induces decay of distinct microRNA families.Cell reports · 2025Article
- LncRNA NRAD1 regulates the triple-negative breast cancer transcriptome by miRNA biogenesis, localization, and predominately non-ceRNA interactions.Scientific reports · 2025Article
- Sequence, structure, and affinity of miR-34a binding sites determine repression efficacy.Nucleic acids research · 2025Article
- Mapping effective microRNA pairing beyond the seed using abasic modifications.Nucleic acids research · 2025Article
- Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials.Pharmaceutics · 2025Review
- Mechanistic studies ofFrontiers in oncology · 2025Article
- An endogenous cluster of target-directed microRNA degradation sites induces decay of distinct microRNA families.bioRxiv : the preprint server for biology · 2024Article
- Elucidating microRNA-34a organisation within human Argonaute-2 by dynamic nuclear polarisation-enhanced magic angle spinning NMR.Nucleic acids research · 2024Article
- Spatiotemporal Control of microRNA-Target Interactions.Wiley interdisciplinary reviews. RNAReview
- Target-directed microRNA degradation: Mechanisms, significance, and functional implications.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs (miRNAs) are short RNAs that post-transcriptionally regulate gene expression by binding to specific sites in mRNAs. Site recognition is primarily mediated by the seed region (nucleotides g2-g8 in the miRNA), but pairing beyond the seed (3'-pairing) is important for some miRNA:target interactions. Here, we use SHAPE, luciferase reporter assays and transcriptomics analyses to study the combined effect of 3'-pairing and secondary structures in mRNAs on repression efficiency. Using the interaction between miR-34a and its SIRT1 binding site as a model, we provide structural and functional evidence that 3'-pairing can compensate for low seed-binding site accessibility, enabling repression of sites that would otherwise be ineffective. We show that miRNA 3'-pairing regions can productively base-pair with nucleotides far upstream of the seed-binding site and that both hairpins and unstructured bulges within the target site are tolerated. We use SHAPE to show that sequences that overcome inaccessible seed-binding sites by strong 3'-pairing adopt the predicted structures and corroborate the model using luciferase assays and high-throughput modelling of 8177 3'-UTR targets for six miRNAs. Finally, we demonstrate that PHB2, a target of miR-141, is an inaccessible target rescued by efficient 3'-pairing. We propose that these results could refine predictions of effective target sites.
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Registered trials
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.