ArticleRNA (New York, N.Y.)2015
Mathematical modeling of combinatorial regulation suggests that apparent positive regulation of targets by miRNA could be an artifact resulting from competition for mRNA.
Article in RNA (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Modulations of obesity-related microRNAs after exercise intervention: a systematic review and bioinformatics analysis.Molecular biology reports · 2021Pooled it
- Data-driven model reveals increased stability of CAG-expanded huntingtin RNA due to MID1 binding.PLoS computational biology · 2026Article
- Competition effects regulating the composition of the microRNA pool.Journal of the Royal Society, Interface · 2025Article
- Integrated mRNA and miRNA analysis reveals the regulatory network of oxidative stress and inflammation in Coilia nasus brains during air exposure and salinity mitigation.BMC genomics · 2024Article
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- Tight junctions and their regulation by non-coding RNAs.International journal of biological sciences · 2021Review
- Biological Pathway Specificity in the Cell-Does Molecular Diversity Matter?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity.International journal of molecular sciences · 2018Review
- Stochastic Modeling of Gene Regulation by Noncoding Small RNAs in the Strong Interaction Limit.Biophysical journal · 2018Article
- Article
- Understanding microRNA-mediated gene regulatory networks through mathematical modelling.Nucleic acids research · 2016Article
- Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis.Frontiers in oncology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs bind to and regulate the abundance and activity of target messenger RNA through sequestration, enhanced degradation, and suppression of translation. Although miRNA have a predominantly negative effect on the target protein concentration, several reports have demonstrated a positive effect of miRNA, i.e., increase in target protein concentration on miRNA overexpression and decrease in target concentration on miRNA repression. miRNA-target pair-specific effects such as protection of mRNA degradation owing to miRNA binding can explain some of these effects. However, considering such pairs in isolation might be an oversimplification of the RNA biology, as it is known that one miRNA interacts with several targets, and conversely target mRNA are subject to regulation by several miRNAs. We formulate a mathematical model of this combinatorial regulation of targets by multiple miRNA. Through mathematical analysis and numerical simulations of this model, we show that miRNA that individually have a negative effect on their targets may exhibit an apparently positive net effect when the concentration of one miRNA is experimentally perturbed by repression/overexpression in such a multi-miRNA multitarget situation. We show that this apparent unexpected effect is due to competition and will not be observed when miRNA interact noncompetitively with the target mRNA. This result suggests that some of the observed unusual positive effects of miRNA may be due to the combinatorial complexity of the system rather than due to any inherently unusual positive effect of the miRNA on its target.
Indexed as
Identifiers
What OpenQuestion holds
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.