ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis

Xiong, Mengneng; Yin, Lisha; Gui, Yiqian; Lv, Chunyu; Ma, Xixiang; Guo, Shuangshuang; Wu, Yanqing; Feng, Shenglei; Fan, Xv; Zhou, Shumin; Wang, Lingjuan; Wen, Yujiao; Wang, Xiaoli; Xie, Qingzhen; Namekawa, Satoshi H.; Yuan, Shuiqiao

doi:10.1083/jcb.202206067

Cited by 4 publications

(3 citation statements)

References 81 publications

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“…Based on protein composition and mitochondrial association of the small granules it seems likely they function in some aspect of piRNA biology. Supporting this notion, two recent reports have demonstrated ADAD2 influences piRNA biogenesis in a manner very similar to RNF17, likely via the interaction between the two proteins [ 68 , 69 ]. However, the IMC is the only definitively known site for piRNA processing in meiotic male germ cells [ 14 ], yet a subset of small ADAD2-RNF17 granules are clearly separate from mitochondria, demonstrating them to be independent of the IMC.…”

Section: Discussionmentioning

confidence: 86%

Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association

et al. 2023

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Mammalian male germ cell differentiation relies on complex RNA biogenesis events, many of which occur in non-membrane bound organelles termed RNA germ cell granules that are rich in RNA binding proteins (RBPs). Though known to be required for male germ cell differentiation, we understand little of the relationships between the numerous granule subtypes. ADAD2, a testis specific RBP, is required for normal male fertility and forms a poorly characterized granule in meiotic germ cells. This work aimed to understand the role of ADAD2 granules in male germ cell differentiation by clearly defining their molecular composition and relationship to other granules. Biochemical analyses identified RNF17, a testis specific RBP that forms meiotic male germ cell granules, as an ADAD2-interacting protein. Phenotypic analysis of Adad2 and Rnf17 mutants identified a rare post-meiotic chromatin defect, suggesting shared biological roles. ADAD2 and RNF17 were found to be dependent on one another for granularization and together form a previously unstudied set of germ cell granules. Based on co-localization studies with well-characterized granule RBPs and organelle-specific markers, a subset of the ADAD2-RNF17 granules are found to be associated with the intermitochondrial cement and piRNA biogenesis. In contrast, a second, morphologically distinct population of ADAD2-RNF17 granules co-localized with the translation regulators NANOS1 and PUM1, along with the molecular chaperone PDI. These large granules form a unique funnel-shaped structure that displays distinct protein subdomains and is tightly associated with the endoplasmic reticulum. Developmental studies suggest the different granule populations represent different phases of a granule maturation process. Lastly, a double Adad2-Rnf17 mutant model suggests the interaction between ADAD2 and RNF17, as opposed to loss of either, is the likely driver of the Adad2 and Rnf17 mutant phenotypes. These findings shed light on the relationship between germ cell granule pools and define new genetic approaches to their study.

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Section: Discussionmentioning

confidence: 86%

Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association

et al. 2023

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“…piRNA pathway components were also recently reported to associate with P-bodies in adult mouse spermatocytes. At that stage, the piRNA ping pong amplification cycle is repressed, in part by the Tudor domain containing protein RNF17 and its interacting protein ADAD2 [ 118 , 127 ]. RNF17 and ADAD2 localize to P-bodies (identified by the P-body markers EDC3 and DCP1a).…”

Section: Stem Cells and Differentiating Germ Cellsmentioning

confidence: 99%

“…RNF17 and ADAD2 localize to P-bodies (identified by the P-body markers EDC3 and DCP1a). Upon knockout of rnf17 or adad2 , aberrant ping-pong occurs, leading to spermatogenesis arrest, and interestingly, a failure of P-bodies to assemble in diplotene spermatocytes [ 127 ]. In C. elegans , a recent preprint reports that P-body like condensates assemble at the periphery of nuage in meiotic germ cells and are required for small RNA homeostasis and transgenerational inheritance [ 31 ].…”

Section: Stem Cells and Differentiating Germ Cellsmentioning

confidence: 99%

P-body-like condensates in the germline

Cassani

Seydoux

2024

Seminars in Cell & Developmental Biology

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Functions and mechanism of noncoding RNA in regulation and differentiation of male mammalian reproduction

Karoii

Azizi

2023

Cell Biochemistry & Function

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Noncoding RNAs (ncRNAs) are active regulators of a wide range of biological and physiological processes, including the majority of mammalian reproductive events. Knowledge of the biological activities of ncRNAs in the context of mammalian reproduction will allow for a more comprehensive and comparative understanding of male sterility and fertility. In this review, we describe recent advances in ncRNA‐mediated control of mammalian reproduction and emphasize the importance of ncRNAs in several aspects of mammalian reproduction, such as germ cell biogenesis and reproductive organ activity. Furthermore, we focus on gene expression regulatory feedback loops including hormones and ncRNA expression to better understand germ cell commitment and reproductive organ function. Finally, this study shows the role of ncRNAs in male reproductive failure and provides suggestions for further research.

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ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis

Cited by 4 publications

References 81 publications

Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association

Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association

P-body-like condensates in the germline

Functions and mechanism of noncoding RNA in regulation and differentiation of male mammalian reproduction

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