Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430.
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.
Pubmed ID: 17761850 RIS Download
3' Untranslated Regions | Animals | Embryo, Nonmammalian | Embryonic Development | Gene Expression Regulation | Left-Right Determination Factors | MicroRNAs | Mutation | Nodal Protein | Nodal Signaling Ligands | RNA, Messenger | Transforming Growth Factor beta | Zebrafish | Zebrafish Proteins