A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Martinez NJ,Ow MC,Barrasa MI,Hammell M,Sequerra R,Doucette-Stamm L,Roth FP,Ambros VR,Walhout AJ

doi

10.1101/gad.1678608

subject

Has Abstract

pub_date

2008-09-15 00:00:00

pages

2535-49

issue

18

eissn

0890-9369

issn

1549-5477

pii

22/18/2535

journal_volume

22

pub_type

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