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Three distinct piRNA populations are present during mouse spermatogenesis: fetal piRNAs in fetal\/perinatal testes, pre-pachytene and pachytene piRNAs in postnatal testes. PNLDC1 is required for piRNA 3\u2019 end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3\u2019 trimming of different piRNA populations in spermatogenesis in mammals remain unclear. Here, by inactivating\n                    <jats:italic>Pnldc1<\/jats:italic>\n                    exonuclease activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in mice, we reveal that the PNLDC1 trimmer activity is essential for spermatogenesis and male fertility. PNLDC1 catalytic activity is required for both fetal and postnatal piRNA 3\u2019 end trimming. Despite this, postnatal piRNA trimming but not fetal piRNA trimming is critical for LINE1 transposon silencing. Furthermore, conditional inactivation of\n                    <jats:italic>Pnldc1<\/jats:italic>\n                    in postnatal germ cells causes LINE1 transposon de-repression and spermatogenic arrest in mice, indicating that germline-specific postnatal piRNA trimming is essential for transposon silencing and germ cell development. Our findings highlight the germ cell-intrinsic role of PNLDC1 and piRNA trimming in mammals to safeguard the germline genome and promote fertility.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011429","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T13:33:48Z","timestamp":1727098428000},"page":"e1011429","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Chao","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyuan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey 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