Major concepts of piRNA biogenesis revealed by the analysis of Shutdown, a co-chaperone with essential roles in the biogenesis of all Drosophila piRNA populations

In animal gonads, 23-30nt long PIWI interacting RNAs (piRNAs) guarantee genome integrity by guiding the sequence specific silencing of selfish genetic elements such as transposons. Two major branches of piRNA biogenesis, namely primary processing and ping-pong amplification, feed into the PIWI clade of Argonaute proteins. Despite our conceptual understanding of piRNA biogenesis, major gaps exist in the mechanistic understanding of the underlying molecular processes as well as in the knowledge of the involved players. Here, we demonstrate an essential role for the female sterility gene shutdown in the piRNA pathway. Shutdown, an evolutionarily conserved co-chaperone of the immunophilin class is the first piRNA biogenesis factor that is essential for all primary and secondary piRNA populations in Drosophila. Based on these findings, we define distinct groups of piRNA biogenesis factors and reveal the core concept of how PIWI family proteins are hard-wired into piRNA biogenesis processes. Overall design: small-RNA libraries from 2 control samples and 7 knock-down samples of D. mel. ovaries and 2 small-RNA profiles from Piwi IP and Aub IP from OSCs.

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Olivieri D, Senti KA, Subramanian S, Sachidanandam R, Brennecke J