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Originally published in Science Express on 24 November 2005
Science 16 December 2005:
Vol. 310. no. 5755, pp. 1817 - 1821
DOI: 10.1126/science.1121158
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Reports

The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution

Kyle Kai-How Farh,1* Andrew Grimson,1* Calvin Jan,1 Benjamin P. Lewis,1,2 Wendy K. Johnston,1 Lee P. Lim,3 Christopher B. Burge,2 David P. Bartel1{dagger}

Thousands of mammalian messenger RNAs are under selective pressure to maintain 7-nucleotide sites matching microRNAs (miRNAs). We found that these conserved targets are often highly expressed at developmental stages before miRNA expression and that their levels tend to fall as the miRNA that targets them begins to accumulate. Nonconserved sites, which outnumber the conserved sites 10 to 1, also mediate repression. As a consequence, genes preferentially expressed at the same time and place as a miRNA have evolved to selectively avoid sites matching the miRNA. This phenomenon of selective avoidance extends to thousands of genes and enables spatial and temporal specificities of miRNAs to be revealed by finding tissues and developmental stages in which messages with corresponding sites are expressed at lower levels.

1 Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3 Rosetta Inpharmatics, 401 Terry Avenue North, Seattle, WA 98109, USA.

* 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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