The silencing or lack of silencing is permanent, they found. If the piRNA doesn't silence a gene the first time it encounters it, it won't ever silence it. And if it silences it once, then every time that gene appears in the future, the system will turn it off.
"This is really remarkable," says Mello. "It implies that an organism has a memory of all the previous gene sequences it's ever expressed before."
The researchers think that the snippets of piRNA do not hold the memory in their sequences. Rather, two other small RNA pathways are thought to provide epigenetic memories of "self" and "non-self" RNA. Mello says piRNAs likely allow mismatched pairing as they scan, so that virtually they can potentially recognize all sequences that have been expressed. Silencing occurs only when a sequence has not been seen before.
While people have hypothesized that foreign RNA is recognized by cells as foreign based on a particular feature of the moleculelike a structural element or chemical tagthe new results suggest that the recognition may be sequence based.
That's not all Mello's lab discovered about piRNAs. Not only did the gene silencing pattern that they establish persist throughout an organism's life, but the memory was passed very stably between generations.
"These small RNAs are present in the germline at all stages and are transmitted to both the egg and the sperm," says Mello.
When genetically identical animals exhibit opposite and heritable phenotypes, the mechanism of inheritance is dubbed epigenetic. In this case, the inducers of epigenetic silencing are piRNAs, so with that in mind, Mello coined the term RNAe, for RNA-induced epigenetic silencing.
A last highlight of the team's findings was that although an organism retains its pattern of piRNA silencing throughout its lifetime, each individual establishes its own pattern. While one may silence a gene everytime it encounters it, another may allo
|Contact: Jennifer Michalowski|
Howard Hughes Medical Institute