‘Junk DNA’ May Help Yeast Survive Stress

After initially dismissing them as junk, researchers have recently begun to
identify some of these roles.

Like deleted scenes snipped out of a movie, some sequences in our genes end up on the cutting-room floor, and cells don’t use them to make proteins. Now, two studies find that these segments, known as introns, help yeast survive during hard times. The research uncovers another possible function for a type of DNA that scientists once thought was useless.

“They are very strong, very convincing, and very exciting results,” says evolutionary molecular biologist Scott Roy of San Francisco State University in California, who wasn’t connected to the studies. The research “opens a whole new paradigm of what introns could be doing.” It also answers the long-standing question of why yeast has kept what was formerly considered “junk DNA,” says yeast microbiologist Guillaume Chanfreau of the University of California, Los Angeles.

Introns are prevalent in plants and fungi, as well as in humans and other animals—each of our roughly 20,000 genes carries an average of eight. When one of our cells starts to make a protein from a particular gene, enzymes generate an RNA copy that includes the introns. Next, the cell snips the introns out of the RNA and splices the remaining portions of the molecule back together. This edited RNA molecule then serves as a guide to build the protein. Removing introns requires a lot of energy—and a complex set of molecular shears suggesting the sequences evolved to carry out specific functions. After initially dismissing them as junk, researchers have recently begun to identify some of these roles. For instance, introns in some genes may help control how much of the corresponding proteins the cell manufactures. But in baker’s yeast, an organism that has ditched most of its introns (it has just 295 for some 6000 genes), the functions of most of the sequences are murky. Scientists who deleted individual introns, for example, found that in most cases the fungi were unfazed.
However, researchers typically haven’t looked at yeast under conditions it would face in the wild, where it could endure periods of food scarcity that don’t occur in the lab. To determine what happens during deprivation, RNA biologist Sherif Abou Elela of the University of Sherbrooke in Canada and colleagues systematically deleted introns from yeast, producing hundreds of strains, each of which was missing all of the introns from one gene. The researchers then grew combinations of these modified strains alongside normal fungi. When food was scarce, most of the intron-lacking strains rapidly died out, the team reports today in Nature. They couldn’t compete with normal yeast. However, in cultures with more nutrients, the altered yeast had the advantage. “If you are in good times, it’s a burden” to have introns, Abou Elela says. “In bad times, it’s beneficial.” Molecular biologist David Bartel of the Massachusetts Institute of Technology in Cambridge and colleagues independently chanced on similar results. They were measuring the amounts of different RNA molecules in yeast cells, and they expected most introns to quickly deteriorate after they were snipped out of their parental RNA strand. But as they report today in a separate paper in Nature, they noticed that large numbers of introns built up in cells growing in crowded cultures. “It was incredibly bizarre,” says Bartel’s former graduate student Jeffrey Morgan, now a molecular biologist at the University of Utah in Salt Lake City. Like Abou Elela’s team,
Bartel’s group found that introns aided yeast under duress but harmed cells living under more favorable conditions. The scientists suspect the introns help the stressed-out yeast rein in growth. Although how these introns provide their benefits remains unclear, the two studies suggest similar mechanisms. As the yeast’s environment turns harsh, introns become more abundant and may effectively clog the molecular shears that normally snip them out of RNAs, slowing down the synthesis of some proteins and allowing the cells to conserve their resources. That may seem like a convoluted process, but “evolution doesn’t always choose the simplest solution,” Bartel says.
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