Goodier, J. L. & Kazazian, H. H. Jr Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135, 23–35 (2008).
Kojima, K. K., Seto, Y. & Fujiwara, H. The wide distribution and change of target specificity of R2 non-LTR retrotransposons in animals. PLoS ONE 11, e0163496 (2016).
Eickbush, D. G., Burke, W. D. & Eickbush, T. H. Evolution of the R2 retrotransposon ribozyme and its self-cleavage site. PLoS ONE 8, e66441 (2013).
Kojima, K. K. & Fujiwara, H. Long-term inheritance of the 28S rDNA-specific retrotransposon R2. Mol. Biol. Evol. 22, 2157–2165 (2005).
Fujiwara, H. et al. Introns and their flanking sequences of Bombyx mori rDNA. Nucleic Acids Res. 12, 6861–6869 (1984).
Roiha, H., Miller, J. R., Woods, L. C. & Glover, D. M. Arrangements and rearrangements of sequences flanking the two types of rDNA insertion in D. melanogaster. Nature 290, 749–754 (1981).
Kojima, K. K. & Fujiwara, H. Evolution of target specificity in R1 clade non-LTR retrotransposons. Mol. Biol. Evol. 20, 351–361 (2003).
Burke, W. D., Malik, H. S., Lathe, W. C. III & Eickbush, T. H. Are retrotransposons long-term hitchhikers? Nature 392, 141–142 (1998).
Malik, H. S., Burke, W. D. & Eickbush, T. H. The age and evolution of non-LTR retrotransposable elements. Mol. Biol. Evol. 16, 793–805 (1999).
Eickbush, T. H. in Mobile DNA II (eds Craig, N. L. et al.) 813–835 (ASM, 2002).
Fujiwara, H. in Mobile DNA III (eds Chandler, M. et al.) 1147–1163 (ASM, 2015).
Eickbush, T. H. & Eickbush, D. G. Integration, regulation, and long-term stability of R2 retrotransposons. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.mdna3-0011-2014 (2015).
Christensen, S. M. & Eickbush, T. H. R2 target-primed reverse transcription: ordered cleavage and polymerization steps by protein subunits asymmetrically bound to the target DNA. Mol. Cell. Biol. 25, 6617–6628 (2005).
Han, J. S. Non-long terminal repeat (non-LTR) retrotransposons: mechanisms, recent developments, and unanswered questions. Mob. DNA 1, 15 (2010).
Zhang, X. et al. Harnessing eukaryotic retroelement proteins for transgene insertion into human safe-harbor loci. Nat. Biotechnol. 43, 42–51 (2025).
Kuroki-Kami, A. et al. Targeted gene knockin in zebrafish using the 28S rDNA-specific non-LTR-retrotransposon R2Ol. Mob. DNA 10, 23 (2019).
Su, Y., Nichuguti, N., Kuroki-Kami, A. & Fujiwara, H. Sequence-specific retrotransposition of 28S rDNA-specific LINE R2Ol in human cells. RNA 25, 1432–1438 (2019).
Chen, Y. et al. All-RNA-mediated targeted gene integration in mammalian cells with rationally engineered R2 retrotransposons. Cell 187, 4674–4689 (2024).
Wilkinson, M. E., Frangieh, C. J., Macrae, R. K. & Zhang, F. Structure of the R2 non-LTR retrotransposon initiating target-primed reverse transcription. Science 380, 301–308 (2023).
Luchetti, A. & Mantovani, B. Non-LTR R2 element evolutionary patterns: phylogenetic incongruences, rapid radiation and the maintenance of multiple lineages. PLoS ONE 8, e57076 (2013).
Kojima, K. K. Structural and sequence diversity of eukaryotic transposable elements. Genes Genet. Syst. 94, 233–252 (2020).
Bao, W., Kojima, K. K. & Kohany, O. Repbase Update, a database of repetitive elements in eukaryotic genomes. Mob. DNA 6, 11 (2015).
Yang, J., Malik, H. S. & Eickbush, T. H. Identification of the endonuclease domain encoded by R2 and other site-specific, non-long terminal repeat retrotransposable elements. Proc. Natl Acad. Sci. USA 96, 7847–7852 (1999).
Bibillo, A. & Eickbush, T. H. End-to-end template jumping by the reverse transcriptase encoded by the R2 retrotransposon. J. Biol. Chem. 279, 14945–14953 (2004).
Ruminski, D. J., Webb, C.-H. T., Riccitelli, N. J. & Lupták, A. Processing and translation initiation of non-long terminal repeat retrotransposons by hepatitis delta virus (HDV)-like self-cleaving ribozymes. J. Biol. Chem. 286, 41286–41295 (2011).
Kong, X. et al. Precise genome editing without exogenous donor DNA via retron editing system in human cells. Protein Cell 12, 899–902 (2021).
Zhao, B., Chen, S.-A. A., Lee, J. & Fraser, H. B. Bacterial retrons enable precise gene editing in human cells. CRISPR J. 5, 31–39 (2022).
Borel, F., Lacroix, F. B. & Margolis, R. L. Prolonged arrest of mammalian cells at the G1/S boundary results in permanent S phase stasis. J. Cell Sci. 115, 2829–2838 (2002).
Anzalone, A. V. et al. Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing. Nat. Biotechnol. 40, 731–740 (2022).
Zheng, C. et al. Template-jumping prime editing enables large insertion and exon rewriting in vivo. Nat. Commun. 14, 3369 (2023).
Wang, J. et al. Efficient targeted insertion of large DNA fragments without DNA donors. Nat. Methods 19, 331–340 (2022).
Yarnall, M. T. N. et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nat. Biotechnol. 41, 500–512 (2023).
de Rocquigny, H. et al. The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr. J. Biol. Chem. 272, 30753–30759 (1997).
Kojima, K. K. & Fujiwara, H. An extraordinary retrotransposon family encoding dual endonucleases. Genome Res. 15, 1106–1117 (2005).
Edgar, R. C. Muscle5: High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny. Nat. Commun. 13, 6968 (2022).
Eddy, S. R. Accelerated profile HMM searches. PLoS Comput. Biol. 7, e1002195 (2011).
Woodcroft, B. J., Boyd, J. A. & Tyson, G. W. OrfM: a fast open reading frame predictor for metagenomic data. Bioinformatics 32, 2702–2703 (2016).
Mistry, J. et al. Pfam: the protein families database in 2021. Nucleic Acids Res. 49, D412–D419 (2021).
Lu, S. et al. CDD/SPARCLE: the conserved domain database in 2020. Nucleic Acids Res. 48, D265–D268 (2020).
Sigrist, C. J. A. et al. New and continuing developments at PROSITE. Nucleic Acids Res. 41, D344–D347 (2013).
Kalvari, I. et al. Rfam 14: expanded coverage of metagenomic, viral and microRNA families. Nucleic Acids Res. 49, D192–D200 (2021).
Nawrocki, E. P. & Eddy, S. R. Infernal 1.1: 100-fold faster RNA homology searches. Bioinformatics 29, 2933–2935 (2013).
Benson, G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 27, 573–580 (1999).
Steinegger, M. & Söding, J. MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. Nat. Biotechnol. 35, 1026–1028 (2017).
Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013).
Steenwyk, J. L., Buida, T. J. III, Li, Y., Shen, X.-X. & Rokas, A. ClipKIT: A multiple sequence alignment trimming software for accurate phylogenomic inference. PLoS Biol. 18, e3001007 (2020).
Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2 – approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490 (2010).
Yu, G. Using ggtree to visualize data on tree-like structures. Curr. Protoc. Bioinformatics 69, e96 (2020).
Valdar, W. S. J. Scoring residue conservation. Proteins 48, 227–241 (2002).
Killick, R. & Eckley, I. A. changepoint: an R package for changepoint analysis. J. Stat. Softw. 58, 1–19 (2014).
Hu, J. et al. Detecting DNA double-stranded breaks in mammalian genomes by linear amplification–mediated high-throughput genome-wide translocation sequencing. Nat. Protoc. 11, 853–871 (2016).
Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10–12 (2011).
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Clement, K. et al. CRISPResso2 provides accurate and rapid genome editing sequence analysis. Nat. Biotechnol. 37, 224–226 (2019).
