Figure 3. Multiplicity and cooperativity of miRNA-target interactions of differentially expressed miRNAs (p< 0.05).

One miRNA can target more than one gene (multiplicity) and one gene can be regulated by more than one miRNA (cooperativity). The distributions for multiplicity and cooperativity were based on (1) log₂ rank of differentially expressed miRNAs vs. number of gene targets (based on targets presented in tables S1-S6), and (2) log₂ rank of gene targets vs. number of miRNAs directed at them, respectively. Multiplicity and cooperativity of differentially over-expressed miRNAs were shown in panels a, c respectively, and differentially under-expressed miRNAs were shown in (b) and (d) respectively. Distributions decayed exponentially. Very few over- and under-expressed miRNAs regulated over 40 predicted targets (top left a-b), but most miRNAs controlled only a few genes (bottom right a-b). A few targets appeared to be under highly cooperative miRNA regulation (top left c-d), but most genes were targeted by fewer than four differentially expressed miRNAs (bottom right c-d).