A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity.
MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegans miRNA regulatory network that contains experimentally mapped transcriptional TF --> miRNA interactions, as well as computationally predicted post-transcriptional miRNA --> TF interactions. We find that this integrated miRNA network contains 23 miRNA <--> TF composite feedback loops in which a TF that controls a miRNA is itself regulated by that same miRNA. By rigorous network randomizations, we show that such loops occur more frequently than expected by chance and, hence, constitute a genuine network motif. Interestingly, miRNAs and TFs in such loops are heavily regulated and regulate many targets. This "high flux capacity" suggests that loops provide a mechanism of high information flow for the coordinate and adaptable control of miRNA and TF target regulons.
Martinez
Natalia J
NJ
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Ow
Maria C
MC
Barrasa
M Inmaculada
MI
Hammell
Molly
M
Sequerra
Reynaldo
R
Doucette-Stamm
Lynn
L
Roth
Frederick P
FP
Ambros
Victor R
VR
Walhout
Albertha J M
AJ
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D016678:Genome; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
D035683:MicroRNAs
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