Modularity and diversity of target selectors in Tn7 transposons

Guilhem Faure; Makoto Saito; Sean Benler; Iris Peng; Yuri I Wolf; Jonathan Strecker; Han Altae-Tran; Edwin Neumann; David Li; Kira S Makarova; Rhiannon K Macrae; Eugene V Koonin; Feng Zhang

doi:10.1016/j.molcel.2023.05.013

Modularity and diversity of target selectors in Tn7 transposons

Mol Cell. 2023 Jun 15;83(12):2122-2136.e10. doi: 10.1016/j.molcel.2023.05.013. Epub 2023 Jun 1.

Authors

Affiliations

¹ Howard Hughes Medical Institute, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA.
³ National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA. Electronic address: koonin@ncbi.nlm.nih.gov.
⁴ Howard Hughes Medical Institute, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: zhang@broadinstitute.org.

Abstract

To spread, transposons must integrate into target sites without disruption of essential genes while avoiding host defense systems. Tn7-like transposons employ multiple mechanisms for target-site selection, including protein-guided targeting and, in CRISPR-associated transposons (CASTs), RNA-guided targeting. Combining phylogenomic and structural analyses, we conducted a broad survey of target selectors, revealing diverse mechanisms used by Tn7 to recognize target sites, including previously uncharacterized target-selector proteins found in newly discovered transposable elements (TEs). We experimentally characterized a CAST I-D system and a Tn6022-like transposon that uses TnsF, which contains an inactivated tyrosine recombinase domain, to target the comM gene. Additionally, we identified a non-Tn7 transposon, Tsy, encoding a homolog of TnsF with an active tyrosine recombinase domain, which we show also inserts into comM. Our findings show that Tn7 transposons employ modular architecture and co-opt target selectors from various sources to optimize target selection and drive transposon spread.

Keywords: CAST; CRISPR; Tn7; mobile elements; transposon; tyrosine recombinase.

MeSH terms

Clustered Regularly Interspaced Short Palindromic Repeats*
DNA Transposable Elements* / genetics
Plasmids
Recombinases / genetics
Tyrosine / genetics

Substances

DNA Transposable Elements
Recombinases
Tyrosine

Grants and funding

R01 HG009761/HG/NHGRI NIH HHS/United States