Table 1.

Summary of key differences between two models in regard to the effect of miRNA:target ratio upon ceRNA crosstalk.

	Bosson et al. (2014)	Denzler et al. (2016)
Model proposed	Hierarchical model where AGO:miRNA complexes are predominantly bound by high affinity target sites	Non-hierarchical model where AGO:miRNA complexes are evenly distributed across all target sites, independent of their affinity
Potential for ceRNA crosstalk	Defined by the ratio of the abundance of miRNA molecules to the number of their high affinity binding sites	Defined by the abundance of miRNA binding sites in the transcriptome
Method of defining the number of additional miRNA binding sites required for target derepression	Data grouped into bins by number of miRNA binding sites added. Derepression threshold defined as the lowest bin at which significant target derepression was observed	Derepression threshold defined as the point at which targets were derepressed by 10% of the total repression observed when no additional binding sites were present
Number of additional miRNA binding sites required for target derepression	miR-294: No derepression observed at 10,800 additional sites	miR-294: 22,000 additional sites
in mouse embryonic stem cells	miR-293: 3000 additional sites	miR-293: 9000 additional sites
	miR-92/25: 3000 additional sites	miR-92/25: 13,000 additional sites
Conclusions	ceRNA crosstalk is possible within physiological conditions provided that the miRNA:target pool ratio is low	ceRNA crosstalk is not possible within physiological conditions