Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression

• DOI: 10.1016/j.molcel.2016.09.027
• Publication Date: 2016-10-27T16:16:46Z
• Authors: Rémy Denzler; Sean E. McGeary; Alexandra C. Title; Vikram Agarwal; David P. Bartel; Markus Stoffel
• Keywords: Competing Endogenous RNA; Derepression

Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent repression, they little effect on magnitude ceRNA expression change required observe derepression. Canonical 6-nt sites, which typically mediate modest can nonetheless compete for binding, with potency ∼20% observed canonical 8-nt In aggregate, low-affinity/background sites also contribute competition. Sites extensive additional complementarity appear as more potent, but only because induce degradation. Cooperative binding proximal same or different miRNAs does increase potency. These results provide quantitative insights into stoichiometric relationship between target abundance, target-site spacing, affinity requirements ceRNA-mediated gene regulation, unusual circumstances in regulation might be observed.