ArticleRNA (New York, N.Y.)2011
Dynamic mechanisms for pre-miRNA binding and export by Exportin-5.
Article in RNA (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
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- Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis.Combinatorial chemistry & high throughput screening · 2024Article
- The role of miRNAs as biomarkers in breast cancer.Frontiers in oncology · 2024Review
- Small molecule-mediated targeting of microRNAs for drug discovery: Experiments, computational techniques, and disease implications.European journal of medicinal chemistry · 2023Review
- Interrelated grid of non-coding RNA: An important aspect in Rheumatoid Arthritis pathogenesis.Molecular biology reports · 2023Review
- Circulating microRNAs as the Potential Diagnostic and Prognostic Biomarkers for Nasopharyngeal Carcinoma.Genes · 2022Review
- Inherent conformational plasticity in dsRBDs enables interaction with topologically distinct RNAs.Biophysical journal · 2022Article
- Mixed-lineage leukemia protein modulates the loading ofHaematologica · 2021Article
- MicroRNAs as Modulators of Oral Tumorigenesis-A Focused Review.International journal of molecular sciences · 2021Review
- Two Putative Cypovirus-Encoded miRNAs Co-regulate the Host Gene of GTP-Binding Nuclear Protein Ran and Facilitate Virus Replication.Frontiers in physiology · 2021Article
- Review
- MicroRNA sequences modulating inflammation and lipid accumulation in macrophage "foam" cells: Implications for atherosclerosis.World journal of cardiology · 2020Review
- Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4.Molecular medicine reports · 2020Article
- Review
- MICROmanagement of Runx2 Function in Skeletal Cells.Current molecular biology reports · 2019Article
- Editorial focus: understanding off-target effects as the key to successful RNAi therapy.Cellular & molecular biology letters · 2019Review
- CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer.International journal of biological sciences · 2019Article
- miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target.Angiogenesis · 2018Review
- Functional Association between Regulatory RNAs and the Annexins.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biogenesis and function of mature microRNAs (miRNAs) is dependent on the nuclear export of miRNA precursors (pre-miRNA) by Exportin-5 (Exp5). To characterize the molecular mechanisms of how pre-miRNA is recognized and transported by Exp5, we have performed 21 molecular dynamic (MD) simulations of RNA-bound Exp5 (Exp5-RanGTP-premiRNA, Exp5-RanGDP-premiRNA, Exp5-premiRNA), RNA-unbound Exp5 (Exp5-RanGTP, Exp5-RanGDP, apo-Exp5), and pre-miRNA. Our simulations with standard MD, steered molecular dynamics (SMD), and energy analysis have shown that (1) Free Exp5 undergoes extensive opening motion, and in this way facilitates the RanGTP binding. (2) RanGTP efficiently regulates the association/dissociation of pre-miRNA to its complex by inducing conformational changes in the HEAT-repeat helix stacking of Exp5. (3) The GTP hydrolysis prevents Ran from rebinding to Exp5 by regulating the hydrophobic interfaces and salt bridges between Ran and Exp5. (4) The transition from the A'-form to the A-form of the pre-miRNA modulates the structural complementarities between the protein and the pre-miRNA, thus promoting efficient assembly of the complex. (5) The base-flipping process (from the closed to the fully flipped state) of the 2-nt 3' overhang is a prerequisite for the pre-miRNA recognition by Exp5, which occurs in a sequence-independent manner as evidenced by the fact that different 2-nt 3' overhangs bind to Exp5 in essentially the same way. And finally, a plausible mechanism of the pre-miRNA export cycle has been proposed explaining how the protein-protein and protein-RNA interactions are coordinated in physiological conditions.
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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.