PNLDC 1, mouse pre‐pi RNA Trimmer, is required for meiotic and post‐meiotic male germ cell development

PIWI ‐interacting RNA s (pi RNA s) are germ cell‐specific small RNA s essential for retrotransposon gene silencing and male germ cell development. In pi RNA biogenesis, the endonuclease Mito PLD /Zucchini cleaves long, single‐stranded RNA s to generate 5′ termini of precursor pi RNA s (pre‐pi RNA s) that are consecutively loaded into PIWI ‐family proteins. Subsequently, these pre‐pi RNA s are trimmed at their 3′‐end by an exonuclease called Trimmer. Recently, poly(A)‐specific ribonuclease‐like domain‐containing 1 ( PNLDC 1) was identified as the pre‐pi RNA Trimmer in silkworms. However, the function of PNLDC 1 in other species remains unknown. Here, we generate Pnldc1 mutant mice and analyze small RNA s in their testes. Our results demonstrate that mouse PNLDC 1 functions in the trimming of both embryonic and post‐natal pre‐pi RNA s. In addition, pi RNA trimming defects in embryonic and post‐natal testes cause impaired DNA methylation and reduced MIWI expression, respectively. Phenotypically, both meiotic and post‐meiotic arrests are evident in the same individual Pnldc1 mutant mouse. The former and latter phenotypes are similar to those of MILI and MIWI mutant mice, respectively. Thus, PNLDC 1‐mediated pi RNA trimming is indispensable for the function of pi RNA s throughout mouse spermatogenesis.