Keynote Speaker

Topic: How Competition Between Nearby piRNA Ping-Pong Shapes Their Production and Ability to Silence Target Transposons

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PIWI-interacting RNAs (piRNAs) are small RNA molecules that help protect the germline genome by silencing transposons—genetic elements that can move around and cause damage. In many animals, piRNAs are generated through a complex cycle called the ping-pong pathway, in which piRNAs not only guide the cleavage of target transposons but also amplify themselves by producing new piRNAs from the cleavage fragments. Despite its complexity, the biological significance of this pathway remains poorly understood. In this study, we compared piRNA sequencing data from two closely related silkworm cell lines that had been separated by continuous cultivation over seven years. We found that the piRNA sequence repertoire became more variable when overall piRNA production was less efficient. Conversely, when piRNA biogenesis was highly efficient, the repertoire remained stable and consistent. Our analysis, supported by mathematical modeling, suggests this variability results from competition between nearby piRNA ping-pong sites on the precursor RNA. This competition helps determine which piRNAs are ultimately produced. Interestingly, it also explains how piRNAs that would poorly match their transposon targets are avoided: piRNAs with low cleavage efficiency tend to fluctuate, whereas those with high cleavage efficiency become stably fixed in the repertoire. Together, these findings show that the piRNA pathway has a built-in capacity for adaptive and fine-tuning. This dynamic regulation helps organisms defend against a wide and evolving array of transposons, illustrating how simple molecular principles—self-amplification and competition—can drive autonomous optimization and lead to powerful biological resilience.