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Science 318 (5848): 271-274

Copyright © 2007 by the American Association for the Advancement of Science

Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430

Wen-Yee Choi,1,2 Antonio J. Giraldez,1,3* Alexander F. Schier1*

Abstract: MicroRNAs (miRNAs) repress hundreds of target messenger RNAs (mRNAs), but the physiological roles of specific miRNA-mRNA interactions remain largely elusive. We report that zebrafish microRNA-430 (miR-430) dampens and balances the expression of the transforming growth factor–ß (TGF-ß) Nodal agonist squint and the TGF-ß Nodal antagonist lefty. To disrupt the interaction of specific miRNA-mRNA pairs, we developed target protector morpholinos complementary to miRNA binding sites in target mRNAs. Protection of squint or lefty mRNAs from miR-430 resulted in enhanced or reduced Nodal signaling, respectively. Simultaneous protection of squint and lefty or absence of miR-430 caused an imbalance and reduction in Nodal signaling. These findings establish an approach to analyze the in vivo roles of specific miRNA-mRNA pairs and reveal a requirement for miRNAs in dampening and balancing agonist/antagonist pairs.

1 Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
2 Developmental Genetics Program, New York University School of Medicine, New York, NY 10016, USA.
3 Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.

* To whom correspondence should be addressed. E-mail: schier{at}fas.harvard.edu; antonio.giraldez{at}yale.edu


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