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

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

doi:10.1007/s11427-023-2390-5

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

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 WuYonggang Zheng, Xiang Dong Fu, Jinsong Li, Rujuan Liu, Guo Hui Li, Mo Fang Liu

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1459-1481
Number of pages	23
Journal	Science China Life Sciences
Volume	66
Issue number	7
DOIs	https://doi.org/10.1007/s11427-023-2390-5
State	Published - Jul 2023

Keywords

PIWI
PIWI-Ins
male fertility
piRNAs
spermatid development
translational activation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Environmental Science
General Agricultural and Biological Sciences

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10.1007/s11427-023-2390-5

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Wang, X., Lin, D. H., Yan, Y., Wang, A. H., Liao, J., Meng, Q., Yang, W. Q., Zuo, H., Hua, M. M., Zhang, F., Zhu, H., Zhou, H., Huang, T. Y., He, R., Li, G., Tan, Y. Q., Shi, H. J., Gou, L. T., Li, D., ... Liu, M. F. (2023). The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility. Science China Life Sciences, 66(7), 1459-1481. https://doi.org/10.1007/s11427-023-2390-5

Wang, X, Lin, DH, Yan, Y, Wang, AH, Liao, J, Meng, Q, Yang, WQ, Zuo, H, Hua, MM, Zhang, F, Zhu, H, Zhou, H, Huang, TY, He, R, Li, G, Tan, YQ, Shi, HJ, Gou, LT, Li, D, Wu, L, Zheng, Y, Fu, XD, Li, J, Liu, R, Li, GH & Liu, MF 2023, 'The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility', Science China Life Sciences, vol. 66, no. 7, pp. 1459-1481. https://doi.org/10.1007/s11427-023-2390-5

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

abstract = "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.",

keywords = "PIWI, PIWI-Ins, male fertility, piRNAs, spermatid development, translational activation",

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

note = "Publisher Copyright: {\textcopyright} 2023, Science China Press.",

year = "2023",

month = jul,

doi = "10.1007/s11427-023-2390-5",

language = "English (US)",

volume = "66",

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journal = "Science China Life Sciences",

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TY - JOUR

T1 - The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility

AU - Wang, Xin

AU - Lin, Di Hang

AU - Yan, Yue

AU - Wang, An Hui

AU - Liao, Jiaoyang

AU - Meng, Qian

AU - Yang, Wen Qing

AU - Zuo, Heng

AU - Hua, Min Min

AU - Zhang, Fengjuan

AU - Zhu, Hongwen

AU - Zhou, Hu

AU - Huang, Tian Yu

AU - He, Rui

AU - Li, Guangyong

AU - Tan, Yue Qiu

AU - Shi, Hui Juan

AU - Gou, Lan Tao

AU - Li, Dangsheng

AU - Wu, Ligang

AU - Zheng, Yonggang

AU - Fu, Xiang Dong

AU - Li, Jinsong

AU - Liu, Rujuan

AU - Li, Guo Hui

AU - Liu, Mo Fang

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - PIWI

KW - PIWI-Ins

KW - male fertility

KW - piRNAs

KW - spermatid development

KW - translational activation

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M3 - Article

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AN - SCOPUS:85162185767

SN - 1674-7305

VL - 66

SP - 1459

EP - 1481

JO - Science China Life Sciences

JF - Science China Life Sciences

IS - 7

ER -

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

Abstract

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