Li, C., Meng, Z., Wen, Q., Yang, W., Xu, Y., Lyu, Y., Guo, Y., Lyu, T., Shen, D., Dou, K. (2025). Translesion DNA polymerases Rev1 and PolH promote LTR-retrotransposon transcription by safeguarding Pol II occupancy in both germline and somatic tissues of Drosophila.  Nucleic Acids Res. 53(17): gkaf903.

FBrf0263450

Research paper

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.

PMC12448915 (PMC) (EuropePMC)