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The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility

文献类型：期刊论文

作者Wang, Xin6,7; Lin, Di-Hang7; Yan, Yue7; Wang, An-Hui8; Liao, Jiaoyang7; Meng, Qian9,10; Yang, Wen-Qing11; Zuo, Heng7; Hua, Min-Min7,12; Zhang, Fengjuan7
刊名SCIENCE CHINA-LIFE SCIENCES
出版日期2023-06-15
页码23
ISSN号1674-7305
关键词PIWI piRNAs PIWI-Ins translational activation spermatid development male fertility
DOI10.1007/s11427-023-2390-5
通讯作者Liu, Rujuan(liurj@shanghaitech.edu.cn) ; Li, Guo-Hui(ghli@dicp.ac.cn) ; Liu, Mo-Fang(mfliu@sibcb.ac.cn)
英文摘要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.
WOS关键词SMALL RNAS ; MOLECULAR-DYNAMICS ; MESSENGER-RNAS ; BINDING-SITES ; BIOGENESIS ; MIWI ; PROTEINS ; PATHWAY ; UBIQUITINATION ; METHYLATION
资助项目National Key Research and Development Program of China[2022YFA1303300] ; National Key Research and Development Program of China[2021YFC2700200] ; National Key Research and Development Program of China[2017YFA0504400] ; Chinese Academy of Sciences[XDB37000000] ; National Natural Science Foundation of China[31830109] ; National Natural Science Foundation of China[31821004] ; National Natural Science Foundation of China[91940305] ; National Natural Science Foundation of China[31961133022] ; National Natural Science Foundation of China[32101037] ; National Natural Science Foundation of China[32271347] ; National Natural Science Foundation of China[21933010] ; National Natural Science Foundation of China[22203089] ; Science and Technology Commission of Shanghai Municipality[17JC1420100] ; Science and Technology Commission of Shanghai Municipality[2017SHZDZX01] ; Science and Technology Commission of Shanghai Municipality[19JC1410200] ; Science and Technology Commission of Shanghai Municipality[21YF1452700] ; Science and Technology Commission of Shanghai Municipality[21ZR1470500] ; Young Elite Scientist Sponsorship Program of the China Association for Science and Technology[2021QNRC001] ; Foundation of Key Laboratory of Gene Engineering of the Ministry of Education
WOS研究方向Life Sciences & Biomedicine - Other Topics
语种英语
出版者SCIENCE PRESS
WOS记录号WOS:001010705800001
源URL[http://119.78.100.183/handle/2S10ELR8/306260]  
专题中国科学院上海药物研究所
通讯作者Liu, Rujuan; Li, Guo-Hui; Liu, Mo-Fang
作者单位1.Ningxia Med Univ, Sch Basic Med Sci, Key Lab Fertil Preservat & Maintenance, Minist Educ, Yinchuan 750004, Peoples R China
2.Ningxia Med Univ, Gen Hosp, Dept Urol, Yinchuan 750004, Peoples R China
3.Cent South Univ, Inst Reprod & Stem Cell Engn, Coll Basic Med, Changsha 410000, Peoples R China
4.Westlake Univ, Sch Life Sci, Westlake Lab Life Sci & Biomed, Hangzhou 310024, Peoples R China
5.Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dept Physiol, Dallas, TX 75390 USA
6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
7.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
8.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式
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,2023:23.
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,23.
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):23.

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来源：上海药物研究所

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