Publication Date
5-1-2023
Journal
Andrology
DOI
10.1111/andr.13400
PMID
36698249
PMCID
PMC10073342
PubMedCentral® Posted Date
5-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Male, Mice, Piwi-Interacting RNA, RNA, Small Interfering, Adenosine Deaminase, Spermatogenesis, Testis, RNA-Binding Proteins
Abstract
BACKGROUND: 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.
OBJECTIVES: This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2.
MATERIALS AND METHODS: Adad2 homozygous mutant mouse lines, Adad2
RESULTS: Adad2–/– and Adad2Δ/Δ mice exhibit male-specific sterility due to 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.
DISCUSSION AND CONCLUSION: In collaboration with RNF17 and other RNA-binding proteins in spermatocytes, ADAD2 directly or indirectly functions in piRNA biogenesis.
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