RT Journal Article
SR Electronic
T1 Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430
JF Science
JO Science
FD American Association for the Advancement of Science
SP 271
OP 274
DO 10.1126/science.1147535
VO 318
IS 5848
A1 Choi, Wen-Yee
A1 Giraldez, Antonio J.
A1 Schier, Alexander F.
YR 2007
UL http://science.sciencemag.org/content/318/5848/271.abstract
AB 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.