How genetic defects in piRNA trimming contribute to male infertility

In germ cells, small non‐coding PIWI‐interacting RNAs (piRNAs) work to silence harmful transposons, maintain genomic stability, and regulate gene expression to ensure fertility. However, these piRNAs must undergo a series of steps during biogenesis to be loaded appropriately onto PIWI proteins and reach the correct nucleotide length. This review is focused on what we are learning about a crucial step in this process, piRNA trimming, in which pre‐piRNAs are shortened to final lengths of 21–35 nucleotides. Recently, the 3’‐5’ exonuclease trimmer has been identified as PNLDC1/PARN‐1. Mutations of the piRNA trimmers in vivo lead to increased transposon expression, elevated levels of untrimmed pre‐piRNAs, decreased piRNA stability and male infertility.