Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.
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March 17 2023
ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis
Mengneng Xiong
,
Mengneng Xiong
*
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
5
Reproductive Medicine Center, Wuhan University Renmin Hospital
, Wuhan, China
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Lisha Yin
,
Lisha Yin
*
(Investigation)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Yiqian Gui
,
Yiqian Gui
*
(Methodology, Software)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Chunyu Lv
,
Chunyu Lv
*
(Conceptualization, Data curation, Formal analysis)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Xixiang Ma
,
Xixiang Ma
(Investigation)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
2
Laboratory of Animal Center, Huazhong University of Science and Technology
, Wuhan, China
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Shuangshuang Guo
,
Shuangshuang Guo
(Resources)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Yanqing Wu
,
Yanqing Wu
(Resources, Visualization)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Shenglei Feng
,
Shenglei Feng
(Investigation)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Xv Fan
,
Xv Fan
(Resources)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Shumin Zhou
,
Shumin Zhou
(Investigation)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Lingjuan Wang
,
Lingjuan Wang
(Investigation, Methodology)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Yujiao Wen
,
Yujiao Wen
(Investigation)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Xiaoli Wang
,
Xiaoli Wang
(Resources, Writing - review & editing)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
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Qingzhen Xie
,
Qingzhen Xie
(Investigation)
5
Reproductive Medicine Center, Wuhan University Renmin Hospital
, Wuhan, China
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Satoshi H. Namekawa
,
Satoshi H. Namekawa
(Writing - review & editing)
3
Department of Microbiology and Molecular Genetics, University of California Davis
, Davis, CA, USA
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Shuiqiao Yuan
(Conceptualization, Funding acquisition, Project administration, Supervision, Visualization, Writing - review & editing)
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
2
Laboratory of Animal Center, Huazhong University of Science and Technology
, Wuhan, China
4
Shenzhen Huazhong University of Science and Technology, Research Institute
, Shenzhen, China
Correspondence to Shuiqiao Yuan: shuiqiaoyuan@hust.edu.cn
Search for other works by this author on:
Mengneng Xiong
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - original draft
*
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
5
Reproductive Medicine Center, Wuhan University Renmin Hospital
, Wuhan, China
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Xixiang Ma
Investigation
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
2
Laboratory of Animal Center, Huazhong University of Science and Technology
, Wuhan, China
Shuangshuang Guo
Resources
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Yanqing Wu
Resources, Visualization
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Shenglei Feng
Investigation
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Xv Fan
Resources
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Shumin Zhou
Investigation
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Lingjuan Wang
Investigation, Methodology
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Yujiao Wen
Investigation
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Xiaoli Wang
Resources, Writing - review & editing
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
Qingzhen Xie
Investigation
5
Reproductive Medicine Center, Wuhan University Renmin Hospital
, Wuhan, China
Satoshi H. Namekawa
Writing - review & editing
3
Department of Microbiology and Molecular Genetics, University of California Davis
, Davis, CA, USA
Shuiqiao Yuan
Conceptualization, Funding acquisition, Project administration, Supervision, Visualization, Writing - review & editing
1
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology
, Wuhan, China
2
Laboratory of Animal Center, Huazhong University of Science and Technology
, Wuhan, China
4
Shenzhen Huazhong University of Science and Technology, Research Institute
, Shenzhen, China
Correspondence to Shuiqiao Yuan: shuiqiaoyuan@hust.edu.cn
*
M. Xiong, L. Yin, Y. Gui, and C. Lv contributed equally to this work.
Disclosures: The authors declare no competing interests exist.
Received:
July 26 2022
Revision Received:
January 04 2023
Accepted:
February 21 2023
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
National Natural Science Foundation of China
- Award Id(s): 82171605,81971444
Funder(s):
Science Technology and Innovation
- Award Id(s): JCYJ20170818160910316
Funder(s):
National Institute of Health
- Award Id(s): GM122776,GM141085
© 2023 Xiong et al.
2023
Xiong et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2023) 222 (5): e202206067.
Article history
Received:
July 26 2022
Revision Received:
January 04 2023
Accepted:
February 21 2023
Citation
Mengneng Xiong, Lisha Yin, Yiqian Gui, Chunyu Lv, Xixiang Ma, Shuangshuang Guo, Yanqing Wu, Shenglei Feng, Xv Fan, Shumin Zhou, Lingjuan Wang, Yujiao Wen, Xiaoli Wang, Qingzhen Xie, Satoshi H. Namekawa, Shuiqiao Yuan; ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis. J Cell Biol 1 May 2023; 222 (5): e202206067. doi: https://doi.org/10.1083/jcb.202206067
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