Translesion DNA polymerases Rev1 and PolH promote LTR-retrotransposon transcription by safeguarding Pol II occupancy in both germline and somatic tissues of Drosophila.

Though typically under strict control, parasitic retrotransposons manage to exploit host factors to proliferate in both germline and somatic cells. Through a genetic screen aimed at identifying host factors for long terminal repeat (LTR)-retrotransposons, we identified translesion DNA polymerases, Rev1 and PolH, as positive regulators of transposons. Rev1 and PolH are interacting partners. Our CUT&Tag data show that they are enriched at active LTR-retrotransposons. Mass spectrometry and proximity ligation assays both indicate that Rev1 associates with RNA polymerase II (Pol II). Furthermore, Pol II chromatin immunoprecipitation (ChIP)-sequencing results show that Rev1 and PolH safeguard Pol II occupancy at LTR-retrotransposons. Given that these active transposons form a high level of R-loops that impede transcription, we propose that Rev1 and PolH safeguard Pol II occupancy at these transcription-challenging elements, thereby facilitating LTR-retrotransposon transcription. Finally, we show that Rev1 and PolH promote retrotransposons in specific somatic tissues of wild-type Drosophila. Our data underscore a unique and critical role for specific translesion DNA polymerases in promoting LTR-retrotransposon transcription, in both germline and somatic tissue. This study may shed light on related researches on retroviruses.