MicroRNAs are tiny snippets of RNA that can repress activity of a gene by targeting the gene's messenger RNA (which copies DNA information and starts the process of protein production).
The first microRNA was discovered in 1993, in worms. It took seven years for the second one to be found, also in worms, but then the floodgates burst. Many microRNAs now have been found in diverse plants and animals, including hundreds in humans. Moreover, microRNAs found in mammals regulate over a third of the human genome, as shown in a 2005 study by the lab of Whitehead Member and Howard Hughes Medical Institute Investigator David Bartel and colleagues.
But given the wealth of microRNAs, and the ability of individual microRNAs to target hundreds of genes, researchers have struggled to show the biological impact of a particular microRNA on a particular target in mammals (although such connections have been shown in plants, worms and flies). Several groups have demonstrated that over-expression or under-expression of a microRNA can play a role in certain cancers, but have not clarified the genes responsible.
Looking to find a promising target for an individual microRNA, Christine Mayr, a postdoctoral researcher in the Bartel lab, picked Hmga2, a gene that is defective in a wide range of tumors.
In these tumors, the protein-producing part of the Hmga2 gene is cut short and replaced with DNA from another chromosome. Biologists have mostly focused on the shortened protein as the possible reason that the cells with this DNA swap became tumors. But this DNA swap removes not only the gene's protein-producing regions but also those areas that don't code for protein. And these non-protein-producing regions contain the elements that microRNAs recognize.
It turns out that in the non-protein-producing region, Hmga2 has seven sites that are complementary to the let-7 microRNA, a microRNA expressed in the later stages of animal development. Mayr wondered whether loss of these let-7 binding sites, and therefore loss of regulation by let-7 of Hmga2, might cause over-expression of Hmga2 that in turn would result in tumor formation.
To find out, Mayr created a series of Hmga2 in which various numbers of let-7 sites were destroyed. She found clear evidence that when exposed to let-7, the fewer sites that were intact, the more protein was produced.
Next, she tested whether disrupting let-7's ability to repress Hmga2 would lead toward tumor creation. In a standard in vitro test of cancer-causing genes, colonies of mouse cells that expressed normal or shortened Hmga2 did not grow significantly, while cells in which Hmga2 contained disrupted let-7 sites did. In fact, the more that let-7 sites were damaged, the greater the number of colonies.
Mayr also worked with MIT assistant professor Michael Hemann to inject these cells in mice with a compromised immune system. The scientists found that the mice with cells that expressed the version of Hmga2 with the disrupted let-7 sites developed tumors.
Overall, the results highlight a new mechanism for cancer formation. Hmga2, and perhaps certain other genes that are normally regulated by microRNAs, can help give rise to tumors if a mutation in the gene disrupts the microRNA's ability to regulate it. In addition, the results show that the interaction of one microRNA with one of its target genes can produce a certain trait in mammals. This is important because scientists are only beginning to learn the functions of microRNAs in animals.
"Because hundreds of human genes appear to be regulated by the let-7 microRNA, we were afraid we wouldn't see any difference when we changed only one of these target genes," says David Bartel, who is also an MIT biology professor. "Seeing the difference encourages us to explore the biological importance of other examples of microRNA regulation."
David Cameron | EurekAlert!
Warming ponds could accelerate climate change
21.02.2017 | University of Exeter
An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
21.02.2017 | Earth Sciences
21.02.2017 | Medical Engineering
21.02.2017 | Trade Fair News