Unravelling the Emerging Paradigms for piRNA‐Target Interaction

ABSTRACT PIWI‐interacting RNAs (piRNAs) have emerged as key gene regulators in diverse biological processes. Earlier believed to be germline‐specific, these endogenous small non‐coding RNAs (~26–32 nucleotides) have now been identified to play an active role in non‐gonadal tissues as well. piRNAs in association with PIWI proteins bind to their targets and form the piRISC complex that especially regulates transposable elements (TEs) in the germline. However, after further experiments, piRNAs have been found to target and modulate the expression of non‐TEs as well. Several high‐throughput technologies have identified piRNA target sites in different cells and tissues of various model organisms, but all these studies have demonstrated discrete patterns of sequence complementarity between piRNA and its target. This indicates that the principle of piRNA targeting is not uniform, unlike miRNAs, due to the lack of precise knowledge regarding their targets. Further, the co‐evolution of the piRNA pathway and its targeted transposons in a species‐specific manner has created distinct differences in the piRNA targeting features between different species, specifically invertebrates and mammals. In this review, we focus on the current high‐throughput techniques that have been used to understand the sequence‐specific features that influence structural conformations favoring piRNA‐target duplex formation and target cleavage. Overall, it has been observed that modulation in the degree of sequence‐based complementarity between piRNA and its target sequence choreographs piRNA target interaction, which in turn enables PIWI to leverage the vast pool of piRNAs in restricting TE escape from surveillance in a sophisticated manner.