PNLDC1 mouse pre‐piRNA Trimmer is required for meiotic and post‐meiotic male germ cell development

摘要

PIWI‐interacting RNAs (piRNAs) are germ cell‐specific small RNAs essential for retrotransposon gene silencing and male germ cell development. In piRNA biogenesis, the endonuclease MitoPLD/Zucchini cleaves long, single‐stranded RNAs to generate 5′ termini of precursor piRNAs (pre‐piRNAs) that are consecutively loaded into PIWI‐family proteins. Subsequently, these pre‐piRNAs are trimmed at their 3′‐end by an exonuclease called Trimmer. Recently, poly(A)‐specific ribonuclease‐like domain‐containing 1 (PNLDC1) was identified as the pre‐piRNA Trimmer in silkworms. However, the function of PNLDC1 in other species remains unknown. Here, we generate Pnldc1 mutant mice and analyze small RNAs in their testes. Our results demonstrate that mouse PNLDC1 functions in the trimming of both embryonic and post‐natal pre‐pi style="fixed-case">RNAs. In addition, pi style="fixed-case">RNA trimming defects in embryonic and post‐natal testes cause impaired style="fixed-case">DNA methylation and reduced style="fixed-case">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 style="fixed-case">MILI and style="fixed-case">MIWI mutant mice, respectively. Thus, style="fixed-case">PNLDC1‐mediated pi style="fixed-case">RNA trimming is indispensable for the function of pi style="fixed-case">RNAs throughout mouse spermatogenesis.