A Translation-Activating Function of MIWI/piRNA During Mouse Spermiogenesis

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Dec 14

PMID 31835033

Citations 83

Authors

Peng Dai

Xin Wang

Lan-Tao Gou

Zhi-Tong Li

Ze Wen

Zong-Gui Chen

Min-Min Hua

Ai Zhong

Lingbo Wang

Haiyang Su

Huida Wan

Kun Qian

Lujian Liao

JinSong Li

Bin Tian

Dangsheng Li

Xiang-Dong Fu

Hui-Juan Shi

Yu Zhou

Mo-Fang Liu

Affiliations

Soon will be listed here.

Abstract

Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3' UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development.

Citing Articles

PIWI proteins and piRNAs: key regulators of stem cell biology.

Claro-Linares F, Rojas-Rios P Front Cell Dev Biol. 2025; 13:1540313.

PMID: 39981094 PMC: 11839606. DOI: 10.3389/fcell.2025.1540313.

Exploring the Characters of Non-Coding RNAs in Spermatogenesis and Male Infertility.

Yan Q, Wang Q Int J Mol Sci. 2025; 26(3).

PMID: 39940895 PMC: 11817410. DOI: 10.3390/ijms26031128.

Germ granule-mediated mRNA storage and translational control.

Pham-Bui H, Lee M RNA Biol. 2025; 22(1):1-11.

PMID: 39895378 PMC: 11810088. DOI: 10.1080/15476286.2025.2462276.

Post-testicular spermatozoa of a marine teleost can conduct cytoplasmic and mitochondrial translation.

Castro-Arnau J, Chauvigne F, Gonzalez A, Finn R, Carrascal M, Cerda J iScience. 2025; 28(1):111537.

PMID: 39801836 PMC: 11719862. DOI: 10.1016/j.isci.2024.111537.

Identification and Functional Analysis of miRNAs in Extracellular Vesicles of Semen Plasma from High- and Low-Fertility Boars.

Chen W, Xie Y, Xu Z, Shang Y, Yang W, Wang P Animals (Basel). 2025; 15(1.

PMID: 39794983 PMC: 11718777. DOI: 10.3390/ani15010040.

References

Marchione R, Leibovitch S, Lenormand J . The translational factor eIF3f: the ambivalent eIF3 subunit. Cell Mol Life Sci. 2013; 70(19):3603-16. PMC: 3771369. DOI: 10.1007/s00018-013-1263-y. View

Langmead B, Trapnell C, Pop M, Salzberg S . Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009; 10(3):R25. PMC: 2690996. DOI: 10.1186/gb-2009-10-3-r25. View

Hofmann M, Abramian D, Millan J . A haploid and a diploid cell coexist in an in vitro immortalized spermatogenic cell line. Dev Genet. 1995; 16(2):119-27. DOI: 10.1002/dvg.1020160205. View

Ingolia N, Brar G, Rouskin S, McGeachy A, Weissman J . The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat Protoc. 2012; 7(8):1534-50. PMC: 3535016. DOI: 10.1038/nprot.2012.086. View

Hu J, Sun F, Handel M . Nuclear localization of EIF4G3 suggests a role for the XY body in translational regulation during spermatogenesis in mice. Biol Reprod. 2017; 98(1):102-114. PMC: 5819848. DOI: 10.1093/biolre/iox150. View

Meistrich M, Hess R . Assessment of spermatogenesis through staging of seminiferous tubules. Methods Mol Biol. 2012; 927:299-307. DOI: 10.1007/978-1-62703-038-0_27. View

Hawthorne S, Busanelli R, Kleene K . The 5' UTR and 3' UTR of the sperm mitochondria-associated cysteine-rich protein mRNA regulate translation in spermatids by multiple mechanisms in transgenic mice. Dev Biol. 2006; 297(1):118-26. DOI: 10.1016/j.ydbio.2006.04.468. View

Gou L, Dai P, Yang J, Xue Y, Hu Y, Zhou Y . Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 2014; 24(6):680-700. PMC: 4042167. DOI: 10.1038/cr.2014.41. View

Kwon Y, Hecht N . Cytoplasmic protein binding to highly conserved sequences in the 3' untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells. Proc Natl Acad Sci U S A. 1991; 88(9):3584-8. PMC: 51496. DOI: 10.1073/pnas.88.9.3584. View

10.

Hasuwa H, Ishino K, Siomi H . Human PIWI (HIWI) is an azoospermia factor. Sci China Life Sci. 2017; 61(3):348-350. DOI: 10.1007/s11427-017-9149-0. View

11.

Sun F, Palmer K, Handel M . Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest of mouse spermatocytes. Development. 2010; 137(10):1699-707. PMC: 2860251. DOI: 10.1242/dev.043125. View

12.

Vourekas A, Alexiou P, Vrettos N, Maragkakis M, Mourelatos Z . Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm. Nature. 2016; 531(7594):390-394. PMC: 4795963. DOI: 10.1038/nature17150. View

13.

Lebedeva S, Jens M, Theil K, Schwanhausser B, Selbach M, Landthaler M . Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell. 2011; 43(3):340-52. DOI: 10.1016/j.molcel.2011.06.008. View

14.

Goh W, Falciatori I, Tam O, Burgess R, Meikar O, Kotaja N . piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis. Genes Dev. 2015; 29(10):1032-44. PMC: 4441051. DOI: 10.1101/gad.260455.115. View

15.

Zhong J, Peters A, Kafer K, Braun R . A highly conserved sequence essential for translational repression of the protamine 1 messenger rna in murine spermatids. Biol Reprod. 2001; 64(6):1784-9. DOI: 10.1095/biolreprod64.6.1784. View

16.

Vasudevan S, Steitz J . AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell. 2007; 128(6):1105-18. PMC: 3430382. DOI: 10.1016/j.cell.2007.01.038. View

17.

Watanabe T, Cheng E, Zhong M, Lin H . Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Res. 2014; 25(3):368-80. PMC: 4352877. DOI: 10.1101/gr.180802.114. View

18.

Kleene K . Connecting cis-elements and trans-factors with mechanisms of developmental regulation of mRNA translation in meiotic and haploid mammalian spermatogenic cells. Reproduction. 2013; 146(1):R1-19. DOI: 10.1530/REP-12-0362. View

19.

Vourekas A, Zheng Q, Alexiou P, Maragkakis M, Kirino Y, Gregory B . Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat Struct Mol Biol. 2012; 19(8):773-81. PMC: 3414646. DOI: 10.1038/nsmb.2347. View

20.

Johnson K, Zecevic A, Kwon E . Protocadherin alpha3 acts at sites distinct from classic cadherins in rat testis and sperm. Biol Reprod. 2003; 70(2):303-12. DOI: 10.1095/biolreprod.103.021758. View