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. 2007 Oct 12;318(5848):271-4.
doi: 10.1126/science.1147535. Epub 2007 Aug 30.

Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430

Wen-Yee Choi  1 , Antonio J Giraldez, Alexander F Schier
Affiliations

Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430

Wen-Yee Choi et al. Science. .

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-beta (TGF-beta) Nodal agonist squint and the TGF-beta 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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