{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lu Y"],"funding":["Eunice Kennedy Shriver National Institute of Child Health and Human Development","NICHD NIH HHS","Takeda Science Foundation","Bill and Melinda Gates Foundation"],"pagination":["698-709"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10073342"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(4)"],"pubmed_abstract":["<h4>Background</h4>Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.<h4>Objectives</h4>This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2.<h4>Materials and methods</h4>Adad2 homozygous mutant mouse lines, Adad2<sup>-/-</sup> and Adad2<sup>Δ/Δ</sup> , were generated by CRISPR/Cas9. Western blotting and immunohistochemistry were used to reveal the expression and subcellular localization of ADAD2. Co-immunoprecipitation tandem mass spectrometry was employed to determine the ADAD2-interacting proteins in mouse testes. RNA-sequencing analyses were carried out to analyze the transcriptome and PIWI-interacting RNA (piRNA) populations in wildtype and Adad2 mutant testes.<h4>Results</h4>Adad2<sup>-/-</sup> and Adad2<sup>Δ/Δ</sup> mice exhibit male-specific sterility because of abnormal spermiogenesis. ADAD2 interacts with multiple RNA-binding proteins involved in piRNA biogenesis, including MILI, MIWI, RNF17, and YTHDC2. ADAD2 co-localizes and forms novel granules with RNF17 in spermatocytes. Ablation of ADAD2 impairs the formation of RNF17 granules, decreases the number of cluster-derived pachytene piRNAs, and increases expression of ping-pong-derived piRNAs.<h4>Discussion and conclusion</h4>In collaboration with RNF17 and other RNA-binding proteins in spermatocytes, ADAD2 directly or indirectly functions in piRNA biogenesis."],"journal":["Andrology"],"pubmed_title":["ADAD2 functions in spermiogenesis and piRNA biogenesis in mice."],"pmcid":["PMC10073342"],"funding_grant_id":["R01HD088412","R01 HD088412","INV‐001902","P01 HD087157","P01HD087157"],"pubmed_authors":["Castaneda JM","Lu Y","Chang HY","Kobayashi H","Kojima-Kita K","Shirane K","Matsuyama M","Kuramochi-Miyagawa S","Koyano T","Nagamori I","Matzuk MM","Yu Z","Ikawa M","Nishimura T"],"additional_accession":[]},"is_claimable":false,"name":"ADAD2 functions in spermiogenesis and piRNA biogenesis in mice.","description":"<h4>Background</h4>Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.<h4>Objectives</h4>This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2.<h4>Materials and methods</h4>Adad2 homozygous mutant mouse lines, Adad2<sup>-/-</sup> and Adad2<sup>Δ/Δ</sup> , were generated by CRISPR/Cas9. Western blotting and immunohistochemistry were used to reveal the expression and subcellular localization of ADAD2. Co-immunoprecipitation tandem mass spectrometry was employed to determine the ADAD2-interacting proteins in mouse testes. RNA-sequencing analyses were carried out to analyze the transcriptome and PIWI-interacting RNA (piRNA) populations in wildtype and Adad2 mutant testes.<h4>Results</h4>Adad2<sup>-/-</sup> and Adad2<sup>Δ/Δ</sup> mice exhibit male-specific sterility because of abnormal spermiogenesis. ADAD2 interacts with multiple RNA-binding proteins involved in piRNA biogenesis, including MILI, MIWI, RNF17, and YTHDC2. ADAD2 co-localizes and forms novel granules with RNF17 in spermatocytes. Ablation of ADAD2 impairs the formation of RNF17 granules, decreases the number of cluster-derived pachytene piRNAs, and increases expression of ping-pong-derived piRNAs.<h4>Discussion and conclusion</h4>In collaboration with RNF17 and other RNA-binding proteins in spermatocytes, ADAD2 directly or indirectly functions in piRNA biogenesis.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-04-21T03:18:27.922Z","creation":"2026-04-21T03:13:51.92Z"},"accession":"S-EPMC10073342","cross_references":{"pubmed":["36698249"],"doi":["10.1111/andr.13400"]}}