Proliferating Cells Foil microRNA Control
News Jun 23, 2008
MIT biologists have discovered that proliferating cells shift the output of their genes to evade regulation by microRNAs, tiny molecules that normally suppress tumor growth.
The work, which could potentially lead to new cancer diagnostics treatments by helping to explain how some cells avoid regulatory controls when they are rapidly dividing, appears in the June 20 issue of Science.
Led by Chris Burge, associate professor of biology and biological engineering, in collaboration with the lab of Institute Professor Phillip Sharp, the researchers studied T lymphocytes, a type of immune cell. Normal T cells start dividing rapidly when they encounter their target antigen (for example, a specific bacterium or virus).
Burge and his colleagues found that when T cells begin dividing, they start producing a shorter version of messenger RNA (mRNA), which carries protein-building instructions transcribed from DNA.
The shorter mRNA is missing about half of a section called the 3' untranslated region (UTR), which does not code for proteins, but contain binding sites for many microRNAs. When those binding sites are missing, the cell is able to escape control by the microRNAs, which generally function to suppress growth.
"When cells proliferate, they change their mRNA in a way that reduces the impact of microRNA regulation," Burge explained.
For normal T cells, that response is desirable; however, in cancerous cells it may not be.
The researchers found the same effect in many other human cell types and tissues, including liver, lung and brain.
Since microRNAs were identified in mammals several years ago, much work has been done on how over- or underexpression of microRNA affects cell proliferation.
Learning more about how mRNAs evade microRNA control could help researchers develop ways to control the mRNA switch from the long form to the short form, so the mRNA remains susceptible to microRNA control, Burge said. The findings could also aid design of small RNA therapeutics, by focusing on targeting those UTR regions that remain unchanged when cells proliferate.