Two studies published in Science reveal that sperm from the rodents carry pieces of RNAs that alter the metabolism of their offspring. The RNAs spotlighted by the studies normally help synthesize proteins, so the findings point to an unconventional form of inheritance.
“Impossible” is exactly how biologists once described so-called epigenetic inheritance, in which something other than a DNA sequence passes a trait between generations. In recent years, however, researchers have found many examples. A male mouse’s diet and stress level, for instance, can tweak offspring metabolism.
Researchers are still trying to determine how offspring inherit a father’s metabolic attributes and physiological condition. Some evidence implicates chemical modification of DNA. Other work by neuroscientist Tracy Bale of the University of Pennsylvania Perelman School of Medicine in Philadelphia and colleagues has found that mammalian sperm pack gene-regulating molecules called microRNAs.
The new work highlights a different class of RNAs, transfer RNAs (tRNAs). In one study, researchers delved into a case of epigenetic inheritance in which the progeny of mice fed a low-protein diet show elevated activity of genes involved in cholesterol and lipid metabolism. When the group analyzed sperm from the protein-deprived males, they uncovered an increased abundance of fragments from several kinds of tRNAs. The researchers concluded the sperm acquired most of these fragments while passing through the epididymis, a duct from the testicle where the cells mature.
In the second study, researchers also homed in on tRNA fragments. After feeding male mice either a high-fat or low-fat diet, the scientists injected the animals’ sperm into unfertilized eggs. They then tracked the metabolic performance of the offspring, which ate a normal diet. Although progeny of the fat-eating fathers remained lean, they showed two abnormalities often found in their dads and in people who are obese or diabetic: abnormal absorption of glucose and insensitivity to insulin. To determine whether tRNA fragments were responsible for the traits, the researchers inserted the fragments into eggs fertilized with other sperm. Fragments that came from fathers that ate the high-fat diet resulted in offspring that also showed impaired glucose absorption.
Although tRNAs are best known for roles in protein synthesis, their fragments are turning up in other cellular situations. Both studies suggest that the RNA bits alter gene activity. Researchers blocked one of the tRNA fragments inside embryonic stem cells and increased the activity of about 70 genes.