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A quantitative understanding of microRNA- mediated competing endogenous RNA regulation |
Ye Yuan,Xinying Ren,Zhen Xie,Xiaowo Wang( ) |
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 |
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Abstract MicroRNA (miRNA) plays key roles in post-transcriptional regulations. Recently, a competing endogenous RNA (ceRNA) hypothesis has been proposed that miRNA targets could communicate and regulate each other through titrating shared miRNAs, which provides a new layer of gene regulation. Though a number of ceRNAs playing biological functions have been identified, the ceRNA hypothesis remains controversial. Recent experimental and theoretical studies argued that the modulation of a single RNA species could hardly change the expression level of competing miRNA targets through ceRNA effect under normal physiological conditions. Here, we reviewed a common framework to model miRNA regulations, and summarized the current theoretical and experimental studies for quantitative understanding ceRNA effect. By revisiting a coarse-grained ceRNA model, we proposed that network topology could significantly influence the competing effect and ceRNA regulation at protein level could be much stronger than that at RNA level. We also provided a conditional independent binding equation to describe miRNA relative repression on different target, which could be applied to quantify siRNA off-target effect.
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Author Summary
MicroRNA (miRNA) plays key roles in post-transcriptional regulations. Recently, a hypothesis of competing endogenous RNA (ceRNA) has been proposed as a new layer of gene regulation. Here, we revisit the common modelling framework and the current understanding of ceRNA effect. We propose that network topology could significantly influence it and the ceRNA effect at protein level could be much stronger than that at RNA level. We also provide a conditional independent binding equation to describe miRNA relative repression on different target, which could be applied to quantify siRNA off-target effect. |
Keywords
microRNA regulation
competing endogenous RNA
molecular titration
quantitative model
complex networks
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Fund: |
Corresponding Author(s):
Xiaowo Wang
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Online First Date: 16 March 2016
Issue Date: 16 March 2016
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