A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity

MicroRNAs (miRNAs) regulate a majority of protein-coding genes, affecting nearly all biological pathways. However, the quantitative dimensions of miRNA-based regulation are not fully understood. In particular, the implications of miRNA target site location, composition rules for multiple target site...

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Bibliographic Details
Main Authors: Gam, Jeremy Jonathan (Contributor), Babb, Jonathan (Contributor), Weiss, Ron (Contributor)
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Massachusetts Institute of Technology. Synthetic Biology Center (Contributor)
Format: Article
Language:English
Published: Nature Publishing Group, 2018-09-12T18:00:24Z.
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Online Access:Get fulltext
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100 1 0 |a Gam, Jeremy Jonathan  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Biological Engineering  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Synthetic Biology Center  |e contributor 
100 1 0 |a Gam, Jeremy Jonathan  |e contributor 
100 1 0 |a Babb, Jonathan  |e contributor 
100 1 0 |a Weiss, Ron  |e contributor 
700 1 0 |a Babb, Jonathan  |e author 
700 1 0 |a Weiss, Ron  |e author 
245 0 0 |a A mixed antagonistic/synergistic miRNA repression model enables accurate predictions of multi-input miRNA sensor activity 
260 |b Nature Publishing Group,   |c 2018-09-12T18:00:24Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/117727 
520 |a MicroRNAs (miRNAs) regulate a majority of protein-coding genes, affecting nearly all biological pathways. However, the quantitative dimensions of miRNA-based regulation are not fully understood. In particular, the implications of miRNA target site location, composition rules for multiple target sites, and cooperativity limits for genes regulated by many miRNAs have not been quantitatively characterized. We explore these aspects of miRNA biology at a quantitative single-cell level using a library of 620 miRNA sensors and reporters that are regulated by many miRNA target sites at different positions. Interestingly, we find that miRNA target site sets within the same untranslated region exhibit combined miRNA activity described by an antagonistic relationship while those in separate untranslated regions show synergy. The resulting antagonistic/synergistic computational model enables the high-fidelity prediction of miRNA sensor activity for sensors containing many miRNA targets. These findings may help to accelerate the development of sophisticated sensors for clinical and research applications. 
520 |a National Institutes of Health (U.S.) (Grant R01CA173712) 
520 |a National Institutes of Health (U.S.) (Grant P50GM098792) 
655 7 |a Article 
773 |t Nature Communications