Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430.
- Resource Type
- Article
- Authors
- Wen-Yee Choi; Giraldez, Antonio J., ; Schier, Alexander F.,
- Source
- Science; 10/12/2007, Vol. 318 Issue 5848, p271-274, 4p, 1 Diagram, 1 Chart, 1 Graph
- Subject
- Zebra danio
RNA
Microstructure
Messenger RNA
Transforming growth factors
Immunomodulators
Animal genetic engineering
Animal genetics
Gene expression
- Language
- ISSN
- 00368075
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-β (TGF-β) Nodal agonist squint and the TGF-β 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. [ABSTRACT FROM AUTHOR]