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A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to investigate the cause of male sterility in<jats:italic>Adad2<\/jats:italic>mutant mice and to understand the molecular functions of ADAD2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p><jats:italic>Adad2<\/jats:italic>homozygous mutant mouse lines,<jats:italic>Adad2<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>and<jats:italic>Adad2<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup>, were generated by CRISPR\/Cas9. Western blotting and immunohistochemistry were used to reveal the expression and subcellular localization of ADAD2. Co\u2010immunoprecipitation tandem mass spectrometry was employed to determine the ADAD2\u2010interacting proteins in mouse testes. RNA\u2010sequencing analyses were carried out to analyze the transcriptome and PIWI\u2010interacting RNA (piRNA) populations in wildtype and<jats:italic>Adad2<\/jats:italic>mutant testes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Adad2<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>and<jats:italic>Adad2<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup>mice exhibit male\u2010specific sterility because of abnormal spermiogenesis. ADAD2 interacts with multiple RNA\u2010binding proteins involved in piRNA biogenesis, including MILI, MIWI, RNF17, and YTHDC2. ADAD2 co\u2010localizes and forms novel granules with RNF17 in spermatocytes. Ablation of ADAD2 impairs the formation of RNF17 granules, decreases the number of cluster\u2010derived pachytene piRNAs, and increases expression of ping\u2010pong\u2010derived piRNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>In collaboration with RNF17 and other RNA\u2010binding proteins in spermatocytes, ADAD2 directly or indirectly functions in piRNA biogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13400","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:58:46Z","timestamp":1674709126000},"page":"698-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["ADAD2 functions in spermiogenesis and piRNA biogenesis in mice"],"prefix":"10.1111","volume":"11","author":[{"given":"Yonggang","family":"Lu","sequence":"first","affiliation":[{"name":"Immunology Frontier Research Center Osaka University Osaka 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