Autonomous Shaping of the piRNA Sequence Repertoire by Competition between Adjacent Ping-Pong Sites

Abstract

PIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements (TEs). In many species, piRNAs are generated via a complex process known as the ping-pong pathway, coupling TE cleavage with piRNA amplification. However, the biological significance of this complexity remains unclear. Here, we systematically compared piRNA profiles in two related silkworm cell lines and found significant changes in their sequence repertoire. Importantly, the changeability of this repertoire negatively correlated with the piRNA biogenesis efficiency, a trend also observed in Drosophila stocks and single silkworm eggs. This can be explained by competition between adjacent ping-pong sites, supported by our mathematical modeling. Moreover, this competition can rationalize how piRNAs autonomously avoid deleterious mismatches to target TEs in silkworms, flies, and mice. These findings unveil the intrinsic plasticity and adaptability of the piRNA system to combat diverse TE sequences and highlight the universal power of competition and self-amplification to drive autonomous optimization.