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

作　　者：Xin Wang Di-Hang Lin Yue Yan An-Hui Wang Jiaoyang Liao Qian Meng Wen-Qing Yang Heng Zuo Min-Min Hua Fengjuan Zhang Hongwen Zhu Hu Zhou Tian-Yu Huang Rui He Guangyong Li Yue-Qiu Tan Hui-Juan Shi Lan-Tao Gou Dangsheng Li Ligang Wu Yonggang Zheng Xiang-Dong Fu Jinsong Li Rujuan Liu Guo-Hui Li Mo-Fang Liu 

机构地区：[1]Key Laboratory of Systems Health Science of Zhejiang Province,School of Life Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou,310024,China [2]State Key Laboratory of Molecular Biology,State Key Laboratory of Cell Biology,Shanghai Key Laboratory of Molecular Andrology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai,200031,China [3]Laboratory of Molecular Modeling and Design,State Key Laboratory of Molecular Reaction Dynamics,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian,116023,China [4]Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [5]School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China [6]NHC Key Lab of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies),Fudan University,Shanghai,200032,China [7]Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,750004,China [8]Department of Urology,General Hospital of Ningxia Medical University,Ningxia Medical University,Yinchuan,750004,China [9]Institute of Reproductive and Stem Cell Engineering,College of Basic of Medicine,Central South University,Changsha,410000,China [10]Department of Physiology,Howard Hughes Medical Institute,University of Texas Southwestern Medical Center,Dallas,TX,75390,USA [11]Westlake Laboratory of Life Sciences and Biomedicine,School of Life Sciences,Westlake University,Hangzhou,310024,China

出　　处：《Science China(Life Sciences)》2023年第7期1459-1481,共23页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2022YFA1303300,2021YFC2700200,2017YFA0504400);Chinese Academy of Sciences(“Strategic Priority Research Program”grants XDB37000000);the National Natural Science Foundation of China(31830109,31821004,91940305,31961133022,32101037,32271347,21933010,22203089);Science and Technology Commission of Shanghai Municipality(17JC1420100,2017SHZDZX01,19JC1410200,21YF1452700,21ZR1470500);the Young Elite Scientist Sponsorship Program of the China Association for Science and Technology(2021QNRC001);the Foundation of Key Laboratory of Gene Engineering of the Ministry of Education。

摘　　要：PIWI-clade proteins harness pi RNAs of 24–33 nt in length.Of great puzzles are how PIWI-clade proteins incorporate pi RNAs of different sizes and whether the size matters to PIWI/pi RNA function.Here we report that a PIWI-Ins module unique in PIWIclade proteins helps define the length of pi RNAs.Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter pi RNAs and causes spermiogenic failure in mice,demonstrating the functional importance of this regulatory module.Mechanistically,we show that longer pi RNAs provide additional complementarity to target m RNAs,thereby enhancing the assembly of the MIWI/e IF3f/Hu R 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 pi RNAs.These findings reveal a critical role of PIWI-Ins-ensured longer pi RNAs in fine-tuning MIWI/pi RNA targeting capacity,proven essential for spermatid development and male fertility.

关 键 词：PIWI piRNAs PIWI-Ins translational activation spermatid development male fertility 

分 类 号：Q75[生物学—分子生物学]