Affiliation:
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.
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.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
1443 articles.
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