A MicroRNA Imparts Robustness against Environmental Fluctuation during Development

Article
A MicroRNA Imparts Robustness against Environmental Fluctuation during Development

Xin Li1, 2, 3, Justin J. Cassidy1, 2, Catherine A. Reinke1, Stephen Fischboeck1 and Richard W. Carthew1, ,

1Department of Biochemistry, Molecular Biology and Cell Biology, 2205 Tech Drive, Northwestern University, Evanston, Illinois 60208, USA


Received 16 May 2008; revised 25 November 2008; accepted 29 January 2009. Published: April 16, 2009. Available online 16 April 2009.

Summary
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 better understand the evolutionary significance of microRNA-target relationships. From studies of two well 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.