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 |