Duncalf, L., Wang, X., Aljabri, A.A., Campbell, A.E., Alharbi, R.Q., Donaldson, I., Hayes, A., Peti, W., Page, R., Bennett, D. (2025). PNUTS:PP1 recruitment to Tox4 regulates chromosomal dispersal in Drosophila germline development.  Cell Rep. 44(5): 115693.

FBrf0262508

Research paper

Ser/Thr protein phosphatase 1 (PP1) forms a large nuclear holoenzyme (with PNUTS, WDR82, and Tox4) whose emerging role is to regulate transcription. However, the role of Tox4, and its interplay with the other phosphatase subunits in this complex, is poorly understood. Here, we combine biochemical, structural, cellular, and in vivo experiments to show that, while tox4 is dispensable for viability, it is essential for fertility, having both PNUTS-dependent and -independent roles in Drosophila germline development. We also show that Tox4 requires zinc for PNUTS TFIIS N-terminal domain (TND) binding, and that it binds the TND on a surface distinct from that used by established TND-interacting transcriptional regulators. We also show that selective disruption of the PNUTS-Tox4 and the PNUTS-PP1 interaction is critical for normal gene expression and chromosomal dispersal during oogenesis. Together, these data demonstrate how interactions within the PNUTS-Tox4-PP1 phosphatase combine to tune transcriptional outputs driving developmental transitions.

PMC12278311 (PMC) (EuropePMC)