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A MicroRNA Imparts Robustness against Environmental Fluctuation during Development
Xin Li1,2,3,Justin J. Cassidy1,2,Catherine A. Reinke1,Stephen Fischboeck1andRichard W. Carthew1,,
1 Department of Biochemistry, Molecular Biology and Cell Biology, 2205 Tech Drive, Northwestern University, Evanston, Illinois 60208, USA
2 These authors contributed equally to this work
3 Present address: Department of Biology, New York University, New York, NY 10003
The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila, in order to betterunderstand the evolutionary significance of microRNA-target relationships. From studies of twowell characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found that miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux. We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks.