title: Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit.
abstract: Competing endogenous RNAs (ceRNAs) cross-regulate each other at the posttranscriptional level by titrating shared microRNAs (miRNAs). Here, we established a computational model to quantitatively describe a minimum ceRNA network and experimentally validated our model predictions in cultured human cells by using synthetic gene circuits. We demonstrated that the range and strength of ceRNA regulation are largely determined by the relative abundance and the binding strength of miRNA and ceRNAs. We found that a nonreciprocal competing effect between partially and perfectly complementary targets is mainly due to different miRNA loss rates in these two types of regulations. Furthermore, we showed that miRNA-like off targets with high expression levels and strong binding sites significantly diminish the RNA interference efficiency, but the effect caused by high expression levels could be compensated by introducing more small interference RNAs (siRNAs). Thus, our results provided a quantitative understanding of ceRNA cross-regulation via shared miRNA and implied an siRNA design strategy to reduce the siRNA off-target effect in mammalian cells.
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and Department of Molecular and Cell Biology, Center for Systems Biology, University of Texas, Dallas, TX 75080-3021.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and.
authors.forename: Yanda
authors.initials: Y
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and xwwang@tsinghua.edu.cn zhenxie@tsinghua.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology/Department of Automation, Tsinghua University, Beijing 100084, China; and xwwang@tsinghua.edu.cn zhenxie@tsinghua.edu.cn.
authors.forename: Xiaowo
authors.initials: X
authors.lastname: Wang
mesh_terms: D053263:Gene Regulatory Networks; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: RNA interference efficiency; competing endogenous RNA; microRNA regulation; quantitative biology; synthetic gene circuits