Review Volume 1, Issue 9 pp 762—770

Figure 3. Possible roles for FFLs of miRNAs, Transcription Factors (TFs) and their mutual targets in facilitating spatiotemporal avoidance, or noise buffering. miRNAs are often embedded in Feed-Forward loops (FFLs) with TFs, sharing mutual targets. It was shown that in many cases during development, miRNAs and their targets avoid expression in the same tissue or at the same developmental stage. This phenome-non was termed "miRNA-target spatiotemporal avoidance". The figure depicts how the network wiring of miRNAs in combined transcriptional/posttranscriptional FFLs may explain the spatio-temporal avoidance phenomenon. Different scenarios may facilitate spatial and temporal avoidance, where the TF and the miRNA are either negatively correlated in their expression across tissues (in A) or positively correlated, namely are expressed in the same tissue (B or C). (A) Spatial avoidance may be facilitated by the presented FFLs when expression of a miRNA and of a TF anti-correlates across tissues. (B) Temporal avoidance may be facilitated by the presented FFL when a miRNA and a TF are co-expressed in the same tissues, creating a temporal shut-down mechanism for their mutual targets, when there is a delay between the activation of the targets by the TF, and its activation of the miRNA. This delay may be achieved for example by a lower affinity binding site of the TF to the miRNA's promoter, by a natural miRNA processing time, etc. (C) Buffering of noise in expression may also be facilitated by a FFL wiring when a miRNA and a TF are co-expressed in the same tissues.