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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Embryo, Nonmammalian / physiology
  • Embryonic Development
  • Gene Expression Regulation
  • Left-Right Determination Factors
  • MicroRNAs / metabolism*
  • Mutation
  • Nodal Protein
  • Nodal Signaling Ligands
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Transforming Growth Factor beta / agonists
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism*
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*


  • 3' Untranslated Regions
  • Left-Right Determination Factors
  • MicroRNAs
  • Nodal Protein
  • Nodal Signaling Ligands
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • lft1 protein, zebrafish
  • ndr1 protein, zebrafish