Sven Klumpe,1,9,* Kirsten A. Senti,2 Florian Beck,1 Jenny Sachweh,3 Bernhard Hampoelz,3 Paolo Ronchi,4 Viola Oorschot,4 Marlene Brandstetter,6 Assa Yeroslaviz,5 John A.G. Briggs,7 Julius Brennecke,2,* Martin Beck,3,8,* and Ju¨ rgen M. Plitzko1,*

1 Research Group CryoEM Technology, Max Planck Institute of Biochemistry, Martinsried, Germany

2 Institute of Molecular Biotechnology Austria (IMBA), Vienna, Austria

3 Department Molecular Sociology, Max Planck Institute of Biophysics, Frankfurt, Germany

4 EMBL EM Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

5 Computational Systems Biochemistry, Bioinformatics Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany

6 Electron Microscopy Facility, Vienna BioCenter Core Facilities, Vienna, Austria

7 Department of Cell and Virus Structure, Max Planck Institute of Biochemistry, Martinsried, Germany

8 Institute of Biochemistry, Goethe University Frankfurt, Frankfurt, Germany

9 Lead contact

*Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (S.K.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (M.B.), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J.M.P.)

https://doi.org/10.1016/j.cell.2025.02.003

SUMMARY

Long terminal repeat (LTR) retrotransposons belong to the transposable elements (TEs), autonomously replicating genetic elements that integrate into the host,s genome. Among animals, Drosophila melanogaster serves as an important model organism for TE research and contains several LTR retrotransposons, including the Ty1-copia family, which is evolutionarily related to retroviruses and forms viruslike particles (VLPs). In this study, we use cryo-focused ion beam (FIB) milling and lift-out approaches to visualize copia VLPs in ovarian cells and intact egg chambers, resolving the in situ copia capsid structure to 7.7 A˚ resolution by cryoelectron tomography (cryo-ET). Although cytoplasmic copia VLPs vary in size, nuclear VLPs are homogeneous and form densely packed clusters, supporting a model in which nuclear import acts as a size selector. Analyzing flies deficient in the TE-suppressing PIWI-interacting RNA (piRNA) pathway, we observe copia,s translocation into the nucleus during spermatogenesis. Our findings provide insights into the replication cycle and cellular structural biology of an active LTR  retrotransposon.