Biology Reference
In-Depth Information
A
miRNA
miRNA
A
A
A
Target
Target
B
B
B
B
miRNA
miRNA
miRNA
Target
Target
Target
A
A
A
C
A
A
TF
TF
TF
TF
miRNA
B
miRNA
miRNA
miRNA
B
C
FFL
C
Target
Target
Target
Target
Simple
regulation
Figure 9.5
MicroRNAs are components of network circuits. (A) Feedback loops
(FBLs) can be double-negative, single-negative, or positive in sign (right). Since
miRNAs repress their targets, then miRNAs can form double-negative or single-
negative FBLs with targets (left). (B) FBLs of any sign can be regulated by a miRNA
that exists outside of the loop. (C) Feedforward loops (FFLs) are distinct from simpler
regulatory circuits (left). MicroRNAs can be components of FFLs, as shown on the
right, where a miRNA is an intermediate in four different FFLs. Two of the FFLs are
coherent, in which each arm of the loop has the same sign. Two of the FFLs are
incoherent since each arm of the loop has the opposite sign.
2.2. Feedback loops and miRNAs
Genome-wide studies have shown that FBLs containing miRNAs are net-
work motifs in
C. elegans
and mammals (
Martinez
et al
., 2008
;
Tsang
et al
.,
2007
). FBLs containing miRNAs can be double-negative, where the miRNA
represses a repressor of the miRNA (
Fig. 9.5
). The double-negative FBLs
containing miRNAs can be associated with bistable dynamics that give rise to
