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MicroRNAs have shaped the evolution of the majority of mammalian genes

mRNAs whose target sequences were not conserved and exposed them to microRNAs, which latched on without a problem. The experiment proved that a matching sequence is generally sufficient to disrupt mRNA's ability to make protein.

But while Grimson showed that, at least in the lab, microRNAs could regulate mRNAs with nonconserved sites, the researchers still didn't know the extent to which nonconserved mRNAs coexisted with their matching microRNAs in the natural cell environment. To answer this question, the researchers turned to gene expression patterns of different types of mouse cells.

Kyle Kai-How Farh, a graduate student in Bartel's lab, found that mRNAs with nonconserved sites were generally absent in cells with corresponding microRNAs--more absent than statistical models suggested. The researchers concluded that over the course of evolution many mRNAs, in order to maintain their functions and ensure fitness of the organism, have quickly lost sites that pair up with microRNAs.

In addition to the thousands of cases where genes have avoided microRNA targeting, Farh also investigated the opposite extreme, cases where genes have maintained microRNA target sites over the course of evolution. He found that as immature muscle cells stop dividing and become mature muscle cells, microRNAs are activated and suppress genes that are no longer needed at such high levels in the mature muscle. "Many of these evolutionarily conserved microRNA targets are known to be active in the processes of cell proliferation, development, and cancer," says Farh. "Our genomes have good reason to maintain the microRNA targeting sites necessary for turning down these genes at the appropriate place and time."

An emerging idea is that microRNAs often act to reduce the quantity of protein a gene produces without shutting it off all together. "We think the microRNAs are sometimes having what you can call a dampening effect," says Bartel, who is also a Howard Hug
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Source:Whitehead Institute for Biomedical Research


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