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MicroRNAs have shaped the evolution of the majority of mammalian genes

RNA continues to shed its reputation as DNA's faithful sidekick. Now, researchers in the lab of Whitehead Institute Member David Bartel have found that a class of small RNAs called microRNAs influence the evolution of genes far more widely than previous research had indicated.

"MicroRNAs are affecting the majority of protein-coding genes, either at a functional level or an evolutionary level," says Andrew Grimson, a post-doctoral fellow in Bartel's lab.

In order to make a protein, a gene codes for a specific molecule called messenger RNA, or mRNA. Each mRNA molecule contains a blueprint for making a protein. A microRNA can bind to a short sequence on a targeted mRNA and suppress protein production.

In a paper published last January in the journal Cell, Bartel's lab, in collaboration with Chris Burge's lab at MIT, presented evidence that one third of human genes are regulated by microRNAs. In this new study, published online Nov. 24 in Science, the researchers demonstrate that microRNAs affect the expression or evolution of the majority of human genes.

Nearly all genes, the authors explain, contain short sequences that match portions of microRNAs. Some of these potential microRNA target sites are evolutionarily "conserved," meaning that they show up in the same spot on the same gene across species as disparate as the mouse and the chicken. The authors of last January's Cell paper showed that thousands of human genes contain microRNA sites that are conserved in this way. To the extent that evolution has preserved these sites more than would be expected by chance, scientists have regarded them as sites that microRNAs target.

But is a matching sequence all that's required for microRNA targeting and gene regulation, and do nonconserved sites also have the potential to disrupt protein production?

In the new study, scientists in the Bartel lab designed an experiment that zeroed in on these nonconserved targets. Grimson took
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Source:Whitehead Institute for Biomedical Research


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