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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

Authors

  • Choi WY
  • Giraldez AJ
  • Schier AF

Journal

Science (New York, N.Y.)

Publication Data

October 12, 2007

Associated Grants

None

Mesh Terms

  • 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