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Published Online August 30, 2007
Science DOI: 10.1126/science.1147535

Reports

Submitted on July 9, 2007
Accepted on August 21, 2007

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

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

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

* To whom correspondence should be addressed.
Antonio J. Giraldez , E-mail: antonio.giraldez{at}yale.edu
Alexander F. Schier , E-mail: schier{at}fas.harvard.edu

MicroRNAs repress hundreds of target mRNAs, but the physiological roles of specific miRNA-mRNA interactions remain largely elusive. We report that zebrafish miR-430 dampens and balances the expression of the TGFß Nodal agonist squint and the TGFß 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.


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