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MicroRNA is a class of short non-coding RNAs that play important posttranscriptional regulatory roles in animals and plants. Each type of microRNA can bind various types of target RNAs. At a certain microRNA expression level, target RNAs could indirectly regulate each other by sequestering shared microRNAs , this phenomenon is called competing endogenous RNAs (ceRNA) effect. The off-target phenomenon in RNAi technology is also closely related to this effect. Through quantitatively describing ceRNA effects, we can have a better understanding towards microRNA regulations and improve the RNAi technology. On March 10th, 2014, Dr. Xiaowo Wang and Dr. Zhen Xie's research group from the Department of Automation at Tsinghua University and Tsinghua National Laboratory for Information Science and Technology published a research paper titled Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit on PNAS. This article systematically analyzed the relationship between microRNA and competing endogenous RNA and it found various factors that could influence its quantitative regulations, therefore they proposed principles to improve RNAi interference technology. Doctoral student Ye Yuan and Research Assistant Bing Liu in the Department of Automation at Tsinghua University were the first co-authors, Dr. Wang and Dr. Xie were the corresponding co-authors. With the combination of systems biology modeling analysis and synthetic biology experiments, this article established a mathematical model to describe the microRNA regulation and built relative synthetic gene circuits in cultured human cells to quantify the ceRNA effect under variable conditions. The results suggested that the ceRNA effect is affected by the abundance of miRNA and ceRNAs, the number and affinity of binding site, and the mRNA degradation pathway determined by the degree of miRNA-mRNA complementarity. Furthermore, a non-reciprocal competing effect of microRNA and RNAi was also demonstrated in this article, while providing a new direction for the improvement of RNAi technology. This work is a successful attempt to reveal the quantitative behavior of gene regulation by combining bioinformatics, systems biology and synthetic biology approaches all together. From Tsinghua news: Xiaowo Wang and Zhen Xie Research Group: Use synthetic gene circuit to reveal the microRNA's quantitative regulation 2015-04-24 20:37:25.0 |
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