Conserved and divergent DNA recognition specificities and functions of R2 retrotransposon N-terminal domains

• DOI: 10.1016/j.celrep.2024.114239
• Publication Date: 2024-05-15T16:56:08Z
• Authors: Rosa Jooyoung Lee; Connor A. Horton; Briana Van Treeck; Jeremy J.R. McIntyre; Kathleen Collins
• Keywords: Retrotransposon

R2 non-long terminal repeat (non-LTR) retrotransposons are among the most extensively distributed mobile genetic elements in multicellular eukaryotes and show promise for applications transgene supplementation of human genome. They insert new gene copies into a conserved site 28S ribosomal DNA with exquisite specificity. clades defined by number zinc fingers (ZFs) at N terminus retrotransposon-encoded protein, postulated to additively confer Here, we illuminate general principles recognition N-terminal domains across between clades, extensive, specific requiring only one or two compact domains. DNA-binding protection assays demonstrate broadly shared as well clade-specific interactions. Gene insertion cells identify sufficient target-site reveal roles second-strand cleavage synthesis ZFs. Our results have implications understanding evolutionary diversification non-LTR retrotransposon mechanisms design retrotransposon-based therapies.