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Numerical modelling of microRNA-mediated mRNA decay identifies novel mechanism of microRNA controlled mRNA downregulation
J. Vohradsky, J. Panek, T. Vomastek,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
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PubMed
20371515
DOI
10.1093/nar/gkq220
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Down-Regulation MeSH
- Humans MeSH
- RNA, Messenger metabolism MeSH
- MicroRNAs metabolism MeSH
- Models, Genetic MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- RNA Stability MeSH
- Gene Silencing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation. miRNAs act by binding to the 3' untranslated region (3'UTR) of an mRNA, affecting the stability and translation of the target mRNA. Here, we present a numerical model of miRNA-mediated mRNA downregulation and its application to analysis of temporal microarray data of HepG2 cells transfected with miRNA-124a. Using the model our analysis revealed a novel mechanism of mRNA accumulation control by miRNA, predicting that specific mRNAs are controlled in a digital, switch-like manner. Specifically, the contribution of miRNAs to mRNA degradation is switched from maximum to zero in a very short period of time. Such behaviour suggests a model of control in which mRNA is at a certain moment protected from binding of miRNA and further accumulates with a basal rate. Genes associated with this process were identified and parameters of the model for all miRNA-124a affected mRNAs were computed.
References provided by Crossref.org
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