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Archive - Jan 15, 2020

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Researchers Develop High-Throughput Method to Study Effects of Removing Hundreds of “Poison Exons” at Same Time; With CRISPR-Based Method, Scientists Show That Poison Exons, Conserved for Over 80 Million Years, Are Essential & Have Anti-Tumor Activity

We don’t have much in common with mice. After 80 million years of diverging evolution, seeing any similarities in our DNA takes some squinting. So, it seems obvious that any bits of DNA that have resisted the forces of evolution and remained identical between mice and humans (and rats and pufferfish) must be critical--probably even essential. Known as “ultra-conserved elements,” these sections of DNA drew immediate scientific attention when the first human genome sequence was released in 2003. And while scientists have discovered some molecular functions for these elements, they have been failing to show their essentiality ever since--until now. In a new study published online on January 7, 2020 in Nature Genetics, scientists at the Fred Hutchinson Cancer Research Center in Seattle, Washington, showed that yes, these ultra-conserved DNA elements are indeed essential. The article is titled “RNA Isoform Screens Uncover the Essentiality and Tumor-Suppressor Activity of Ultraconserved Poison Exons.” Looking at a subclass of ultra-conserved elements known as “poison exons,” the investigators found that certain poison exons were essential for cell growth, while others acted to suppress the growth of lung tumor cells in mice. By showing that ultra-conserved elements operate on a cellular level, these discoveries help shed light on why they have remained unchanged over millions of years. This is the “first study finding large-scale importance of these highly conserved [DNA] elements,” said Dr. Rob Bradley (photo), PhD, a computational biologist and the study’s senior author. The 481 ultra-conserved DNA elements shared between mice, rats, and humans immediately jumped out once these three genomes were sequenced and compared. The finding was “really odd, really interesting,” Dr. Bradley said.