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

被引:402
作者
Choi, Wen-Yee
Giraldez, Antonio J.
Schier, Alexander F.
机构
[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[2] NYU, Sch Med, Dev Genet Program, New York, NY 10016 USA
[3] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA
关键词
D O I
10.1126/science.1147535
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:271 / 274
页数:4
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