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The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility
2023-06-01
发表期刊SCIENCE CHINA-LIFE SCIENCES (IF:8.0[JCR-2023],7.3[5-Year])
ISSN1674-7305
EISSN1869-1889
发表状态已发表
DOI10.1007/s11427-023-2390-5
摘要

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility.

关键词PIWI piRNAs PIWI-Ins translational activation spermatid development male fertility
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收录类别SCI
语种英语
资助项目National Key Research and Development Program of China[
WOS研究方向Life Sciences & Biomedicine - Other Topics
WOS类目Biology
WOS记录号WOS:001010705800001
出版者SCIENCE PRESS
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/316408
专题生命科学与技术学院
生命科学与技术学院_特聘教授组_刘默芳组
生命科学与技术学院_特聘教授组_李劲松组
生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_刘如娟组
共同第一作者Lin, Di-Hang; Yan, Yue; Wang, An-Hui; Liao, Jiaoyang; Meng, Qian; Yang, Wen-Qing
通讯作者Liu, Rujuan; Li, Guo-Hui; Liu, Mo-Fang
作者单位
1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
2.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,State Key Lab Cell Biol,Sha, Shanghai 200031, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
7.Fudan Univ, Shanghai Inst Biomed & Pharmaceut Technol, NHC Key Lab Reprod Regulat, Shanghai 200032, Peoples R China
8.Ningxia Med Univ, Sch Basic Med Sci, Key Lab Fertil Preservat & Maintenance, Minist Educ, Yinchuan 750004, Peoples R China
9.Ningxia Med Univ, Gen Hosp, Dept Urol, Yinchuan 750004, Peoples R China
10.Cent South Univ, Inst Reprod & Stem Cell Engn, Coll Basic Med, Changsha 410000, Peoples R China
11.Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dept Physiol, Dallas, TX 75390 USA
12.Westlake Univ, Sch Life Sci, Westlake Lab Life Sci & Biomed, Hangzhou 310024, Peoples R China
通讯作者单位生命科学与技术学院
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GB/T 7714
Wang, Xin,Lin, Di-Hang,Yan, Yue,et al. The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility[J]. SCIENCE CHINA-LIFE SCIENCES,2023.
APA Wang, Xin.,Lin, Di-Hang.,Yan, Yue.,Wang, An-Hui.,Liao, Jiaoyang.,...&Liu, Mo-Fang.(2023).The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.SCIENCE CHINA-LIFE SCIENCES.
MLA Wang, Xin,et al."The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility".SCIENCE CHINA-LIFE SCIENCES (2023).
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