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Science 304 (5670): 594-596

Copyright © 2004 by the American Association for the Advancement of Science

MicroRNA-Directed Cleavage of HOXB8 mRNA

Soraya Yekta,1,2* I-hung Shih,1* David P. Bartel1,2{dagger}

Abstract: MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs, some of which are known to play important regulatory roles in animals by targeting the messages of protein-coding genes for translational repression. We find that miR-196, a miRNA encoded at three paralogous locations in the A, B, and C mammalian HOX clusters, has extensive, evolutionarily conserved complementarity to messages of HOXB8, HOXC8, and HOXD8. RNA fragments diagnostic of miR-196–directed cleavage of HOXB8 were detected in mouse embryos. Cell culture experiments demonstrated down-regulation of HOXB8, HOXC8, HOXD8, and HOXA7 and supported the cleavage mechanism for miR-196–directed repression of HOXB8. These results point to a miRNA-mediated mechanism for the posttranscriptional restriction of HOX gene expression during vertebrate development and demonstrate that metazoan miRNAs can repress expression of their natural targets through mRNA cleavage in addition to inhibiting productive translation.

1 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dbartel{at}wi.mit.edu

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