Ozata, D. M., Gainetdinov, I., Zoch, A., O’Carroll, D. & Zamore, P. D. PIWI-interacting RNAs: small RNAs with big functions. Nat. Rev. Genet. 20, 89–108 (2019).
Google Scholar
Wang, X., Ramat, A., Simonelig, M. & Liu, M. F. Emerging roles and functional mechanisms of PIWI-interacting RNAs. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-022-00528-0 (2023).
Matsumoto, N. et al. Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA. Cell 167, 484–497.e9 (2016).
Google Scholar
Anzelon, T. A. et al. Structural basis for piRNA targeting. Nature 597, 285–289 (2021).
Google Scholar
Li, Z. et al. Mammalian PIWI–piRNA–target complexes reveal features for broad and efficient target silencing. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01287-6 (2024).
Arif, A. et al. GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins. Nature 608, 618–625 (2022).
Google Scholar
Meister, G. Argonaute proteins: functional insights and emerging roles. Nat. Rev. Genet. https://doi.org/10.1038/nrg3462 (2013).
Aravin, A. et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207 (2006).
Google Scholar
Girard, A., Sachidanandam, R., Hannon, G. J. & Carmell, M. A. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442, 199–202 (2006).
Google Scholar
Grivna, S. T., Beyret, E., Wang, Z. & Lin, H. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 20, 1709–1714 (2006).
Google Scholar
Aravin, A. A., Sachidanandam, R., Girard, A., Fejes-Toth, K. & Hannon, G. J. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316, 744–747 (2007).
Google Scholar
Lewis, S. H. et al. Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements. Nat. Ecol. Evol. https://doi.org/10.1038/s41559-017-0403-4 (2018).
Schnettler, E. et al. Knockdown of piRNA pathway proteins results in enhanced semliki forest virus production in mosquito cells. J. Gen. Virol. 94, 1680–1689 (2013).
Google Scholar
Morazzani, E. M., Wiley, M. R., Murreddu, M. G., Adelman, Z. N. & Myles, K. M. Production of virus-derived ping-pong-dependent piRNA-like small RNAs in the mosquito soma. PLoS Pathog. 8, e1002470 (2012).
Google Scholar
Miesen, P., Girardi, E. & Van Rij, R. P. Distinct sets of PIWI proteins produce arbovirus and transposon-derived piRNAs in Aedes aegypti mosquito cells. Nucleic Acids Res. 43, 6545–6556 (2015).
Google Scholar
Yu, T. et al. The piRNA response to retroviral invasion of the koala genome. Cell https://doi.org/10.1016/j.cell.2019.09.002 (2019).
Brennecke, J. et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128, 1089–1103 (2007).
Google Scholar
Gunawardane, L. S. et al. A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila. Science https://doi.org/10.1126/science.1140494 (2007).
Wu, P. H. et al. The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. Nat. Genet. 52, 728–739 (2020).
Google Scholar
Goh, W. S. S. et al. PiRNA-directed cleavage of meiotic transcripts regulates spermatogenesis. Genes Dev. https://doi.org/10.1101/gad.260455.115 (2015).
Vourekas, A. et al. Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat. Struct. Mol. Biol. 19, 773–781 (2012).
Google Scholar
Zhang, P. et al. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell Res. 25, 193–207 (2015).
Google Scholar
Ohtani, H. et al. DmGTSF1 is necessary for Piwi-piRISC-mediated transcriptional transposon silencing in the Drosophila ovary. Genes Dev. 27, 1656–1661 (2013).
Google Scholar
Dönertas, D., Sienski, G. & Brennecke, J. Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex. Genes Dev. 27, 1693–1705 (2013).
Google Scholar
Yoshimura, T. et al. Mouse GTSF 1 is an essential factor for secondary pi RNA biogenesis. EMBO Rep. https://doi.org/10.15252/embr.201642054 (2018).
Chang, T. H. et al. Maelstrom represses canonical polymerase II transcription within bi-directional piRNA clusters in Drosophila melanogaster. Mol. Cell 73, 291–303.e6 (2019).
Google Scholar
Xiol, J. et al. RNA clamping by Vasa assembles a piRNA amplifier complex on transposon transcripts. Cell 157, 1698–1711 (2014).
Google Scholar
Dai, S. et al. A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing. Cell Rep. 40, 111265 (2022).
Google Scholar
Saxe, J. P., Chen, M., Zhao, H. & Lin, H. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J. 32, 1869–1885 (2013).
Google Scholar
Wei, H. et al. piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis. Nat. Commun. 15, 2343 (2024).
Google Scholar
Song, J. J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Crystal structure of argonaute and its implications for RISC slicer activity. Science 305, 1434–1437 (2004).
Google Scholar
Wang, Y., Sheng, G., Juranek, S., Tuschl, T. & Patel, D. J. Structure of the guide-strand-containing argonaute silencing complex. Nature 456, 209–213 (2008).
Google Scholar
Wang, Y. et al. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921–926 (2008).
Google Scholar
Wang, Y. et al. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature 461, 754–761 (2009).
Google Scholar
Schirle, N. T. & MacR, I. J. The crystal structure of human Argonaute2. Science 336, 1037–1040 (2012).
Google Scholar
Elkayam, E. et al. The structure of human argonaute-2 in complex with miR-20a. Cell 150, 100–110 (2012).
Google Scholar
Nakanishi, K., Weinberg, D. E., Bartel, D. P. & Patel, D. J. Structure of yeast Argonaute with guide RNA. Nature 486, 368–374 (2012).
Google Scholar
Schirle, N. T., Sheu-Gruttadauria, J. & MacRae, I. J. Structural basis for microRNA targeting. Science 346, 608–613 (2014).
Google Scholar
Klum, S. M., Chandradoss, S. D., Schirle, N. T., Joo, C. & MacRae, I. J. Helix‐7 in Argonaute2 shapes the microRNA seed region for rapid target recognition. EMBO J. 37, 75–88 (2018).
Google Scholar
Sheu-Gruttadauria, J. et al. Structural basis for target-directed microRNA degradation. Mol. Cell 75, 1243–1255.e7 (2019).
Google Scholar
Gainetdinov, I. et al. Relaxed targeting rules help PIWI proteins silence transposons. Nature 619, 394–402 (2023).
Google Scholar
Yuan, Y. R. et al. Crystal structure of A. aeolicus Argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol. Cell 19, 405–419 (2005).
Google Scholar
Parker, J. S., Roe, S. M. & Barford, D. Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. EMBO J. 23, 4727–4737 (2004).
Google Scholar
Xiao, Y., Maeda, S., Otomo, T. & MacRae, I. J. Structural basis for RNA slicing by a plant Argonaute. Nat. Struct. Mol. Biol. 30, 778–784 (2023).
Google Scholar
Nakanishi, K. et al. Eukaryote-specific insertion elements control human ARGONAUTE Slicer activity. Cell Rep. 3, 1893–1900 (2013).
Google Scholar
Chen, K. et al. Gtsf1 is essential for proper female sex determination and transposon silencing in the silkworm, Bombyx mori. PLoS Genet. 16, e1009194 (2020).
Google Scholar
Yoshimura, T. et al. Gtsf1/Cue110, a gene encoding a protein with two copies of a CHHC Zn-finger motif, is involved in spermatogenesis and retrotransposon suppression in murine testes. Dev. Biol. 335, 216–227 (2009).
Google Scholar
Muerdter, F. et al. A genome-wide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in drosophila. Mol. Cell 50, 736–748 (2013).
Google Scholar
Almeida, M. V. et al. GTSF‐1 is required for formation of a functional RNA‐dependent RNA Polymerase complex in Caenorhabditis elegans. EMBO J. 37, e99325 (2018).
Google Scholar
Sheu‐Gruttadauria, J., Xiao, Y., Gebert, L. F. & MacRae, I. J. Beyond the seed: structural basis for supplementary micro RNA targeting by human Argonaute2. EMBO J. 38, e101153 (2019).
Google Scholar
Sheng, G. et al. Structure-based cleavage mechanism of Thermus thermophilus argonaute DNA guide strand-mediated DNA target cleavage. Proc. Natl Acad. Sci. USA 111, 652–657 (2014).
Google Scholar
Yamaguchi, S. et al. Crystal structure of Drosophila Piwi. Nat. Commun. 11, 858 (2020).
Google Scholar
Park, M. S. et al. Human Argonaute3 has slicer activity. Nucleic Acids Res. 45, 11867–11877 (2017).
Google Scholar
Park, M. S. et al. Multidomain convergence of Argonaute during RISC assembly correlates with the formation of internal water clusters. Mol. Cell 75, 725–740.e6 (2019).
Google Scholar
Gainetdinov, I. et al. Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability. Mol. Cell 81, 4826–4842.e8 (2021).
Google Scholar
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Google Scholar
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. CryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Google Scholar
Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).
Google Scholar
Wang, N. et al. Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates. Cell 184, 370–383.e13 (2021).
Google Scholar
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. Sect. D. Biol. Crystallogr. https://doi.org/10.1107/S0907444904019158 (2004).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D. Biol. Crystallogr. https://doi.org/10.1107/S0907444909052925 (2010).
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Google Scholar
Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018).
Google Scholar
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
Google Scholar
Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).
Google Scholar
Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).
Google Scholar