Transgenerational epigenetic inheritance--the transfer of nongenetic information picked up during one generation and passed on to the next which may alter the behavior of the recipient--has been of significant interest over the last decade. Now a group from the University of Maryland (UMD) has shown how this might happen, pointing toward RNA being a key player in this transgenerational regulation.
The team, led by Anthony Jose, an assistant professor in the UMD Department of Cell Biology and Molecular Genetics, published the results in the Proceedings of the National Academy of Sciences.
It’s long been appreciated that we are the product of both our parents through the genes they pass down to us. More recently, an area called transgenerational epigenetics has gained momentum after a number of groups have shown that epigenetic marks (for example, DNA methylation) can be altered by an environmental stimulus and inherited. This is important since certain environmental stimuli such as smoking or having a poor diet may leave a “legacy effect” on future offspring.
Jose’s group used Caenorhabditis elegans (C. elegans) as their animal model. The genetics of this worm are well characterized, and importantly, they have a small number of genes, so studying it is simpler than other organisms such as a laboratory mouse.
Double-stranded RNA (dsRNA) are species of noncoding RNA that can silence genes if they share sequence homology and they form one facet of epigenetic regulation. In this study, the researchers showed that certain dsRNA can be transferred between generations in C. elegans, being able to silence genes in the offspring through the transport of them via small, round vesicles.
Interestingly, they also showed that even when the donor parent of the dsRNA is missing the gene with the matching sequence, the dsRNA can still be inherited and silence genes in the offspring, indicating that this regulation can skip generations, leading to a phenomenon of “you are what your grandparents ate” rather than being shaped only by your own lifestyle.
"It's shocking that we can see dsRNA cross generational boundaries," Jose said in a release. "Our results provide a concrete mechanism for how the environment in one generation could affect the next generation. But it's doubly surprising to see that a parent can transmit the information to silence a gene it doesn't have."
"There are hints that similar things could be happening in humans," Jose added. "We know that RNA exists in the human bloodstream. But, we don't know where the RNA molecules are coming from, where they're going or exactly what they're doing. Our work reveals an exciting possibility--they could be messages from parents to their offspring."