Wu, Y., Imai, R., Kosako, H., Nakahara, T., Solberg, T., Siomi, H., Murano, K. (2025). The Piwi-piRNA complex initiates transposon silencing via transcription termination factors PNUTS and Senataxin.  Mol. Cell 85(21): 3999--4015.e8.

FBrf0264061

Research paper

Transcriptional silencing of transposable elements (TEs) is guided by Piwi and PIWI-interacting RNAs (piRNAs) through the SFiNX complex to induce heterochromatin formation. We previously reported that members of the SFiNX complex can induce TE silencing prior to heterochromatin formation, suggesting that Piwi-mediated silencing can be separated into two steps: initiation and maintenance. While many studies have investigated the heterochromatin-dependent maintenance step of TE silencing, the mechanisms underlying silencing initiation remain elusive. In this study, we found that SFiNX can induce silencing independent of H1 and HP1a through an association between the SFiNX-interaction partner Sov and two proteins involved in transcription termination, phosphatase 1 nuclear targeting subunit (PNUTS) and Senataxin. Mechanistically, PNUTS and Senataxin affect the elongation speed or stalling of RNA polymerase II (RNA Pol II) to induce repression. Our findings suggest that piRNAs act as transcription termination signals in the initiation step of piRNA-guided transcriptional repression preceding heterochromatinization of TEs.