Seeing is believing, whether it be a topic as hot as the upcoming presidential election or intergenerational epigenetic effects and transgenerational epigenetic inheritance. While exciting evidence on the role of sperm RNA in mammals has begun to accumulate thanks to the labs of Mansuy, Bale, and Rando, an elegant C. elegans study from the lab of Antony Jose at the University of Maryland brings forth some visually striking RNAi results from the oocyte.
Previously, the Jose lab showed that dsRNA made in the neurons of C. elegans can be transferred to the germline and cause transgenerational gene silencing. The silencing persisted for more than 25 generations without the ancestral source of dsRNA. In their latest work, the Jose lab focused in on the mechanisms of intergenerational transfer. Here’s what went down:
- By feeding worms bacteria with dsRNA, which is then processed by the RNAi pathway into siRNAs that target specific genes (gfp transgenes or unc-22), they observed that the gene silencing effects can skip a generation. This occurs when the mother doesn’t have the target sequence of the dsRNA, as she can still transmit the dsRNA to offspring and if they inherit the target sequence from their father the dsRNA results in gene silencing.
- By labeling gfp-dsRNA with a 5’ fluorophore and injecting it into the mother worms, they found that that dsRNA is imported by endocytosis into oocytes from the extracellular space, along with yolk proteins, which you can see in the video below:
Senior author Antony Jose shares, “This is the first time we’ve seen a dsRNA molecule passing from one generation to the next. It’s shocking that we can see dsRNA cross generational boundaries. But it’s doubly surprising to see that a parent can transmit the information to silence a gene it doesn’t have. One would think the next generation would be protected, but we are seeing all of these dsRNA molecules being dumped into the next generation. Egg cells use the same mechanism to absorb nutrients as they prepare for fertilization. The next generation is not only getting nutrition, it’s also getting information.”
“There are hints that similar things could be happening in humans. 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.”
Catch the full extracellular dsRNA show by transmitting yourself over to PNAS, October 2016