PIWI proteins and piRNAs in pluripotent cells
PIWI proteins and piRNAs are mostly known for their role in transposon silencing during animal germ cell development. piRNAs are small non-coding RNAs that require PIWI proteins for their biogenesis as well as for their silencing activity. A major part of these two processes takes place in a perinuclear structure known as nuage (or chromatoid body or P-granule, depending on the organism).
Typically two different PIWI proteins work together to form a ping-pong cycle that leads to the amplification of piRNAs. As part of this cycle piRNAs guide one PIWI protein to target RNAs using sequence complementarity, triggering the degradation of the target and formation of a new partially complementary piRNA that binds the other PIWI protein. Several other proteins, among which Tudor proteins and Vasa, associate with PIWI proteins and are required for the efficient biogenesis and function of the piRNAs. Some PIWI proteins also have a nuclear function and can mediate epigenetic modification of target DNA, with the help of proteins such as histone methylase HP1 (Drosophila) or DNA methylase Dnmt3 (mouse).
An underappreciated aspect of piRNA biology is that piRNAs - as well as the proteins involved in their biogenesis - have been detected in pluripotent cells in many regenerating animals, ranging from cnidarians to urochordates. Moreover, in each of these systems, loss of PIWI proteins has lead to loss of the pluripotent cells. This suggests that PIWI proteins and piRNAs may play a role in pluripotent cells, e.g. in maintenance of pluripotency or in cell survival.
In S. mediterranea, two PIWI proteins are required for piRNA biosynthesis, and both are essential for animal viability. We use a combination of molecular, cell biological, and genetic approaches to study the role of PIWI proteins and piRNAs in neoblast maintenance and survival.