Host factors that promote retrotransposon integration are similar in distantly related eukaryotes

PLoS Genet. 2017 Dec 12;13(12):e1006775. doi: 10.1371/journal.pgen.1006775. eCollection 2017 Dec.


Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Repair / genetics
  • Eukaryota / genetics
  • Gene Expression Regulation, Fungal
  • Integrases / genetics
  • Integration Host Factors / genetics*
  • Promoter Regions, Genetic
  • RNA-Directed DNA Polymerase / genetics
  • Recombination, Genetic*
  • Retroelements / genetics*
  • Retroviridae / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Schizosaccharomyces / genetics
  • Terminal Repeat Sequences / genetics*
  • Ubiquitin-Protein Ligases / genetics*


  • Integration Host Factors
  • Retroelements
  • Saccharomyces cerevisiae Proteins
  • Spp382 protein, S cerevisiae
  • Rhp18 protein, S pombe
  • Ubiquitin-Protein Ligases
  • Integrases
  • RNA-Directed DNA Polymerase
  • reverse transcriptase Ty3, S cerevisiae

Grant support

This research was supported by the Intramural Research Programs of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.