PPI-Rescue: restoration of eye development via functional reconstitution of a transcription complex.

PPI-Rescue shows that reconstituting the Sine oculis (So)–Eyes Absent (Eya) protein-protein interaction restores transcriptional activity and rescues eye development in Drosophila.

• Why it matters: Genetic perturbations can disrupt all functions of a transcription factor, making it hard to isolate how specific transcription complexes contribute to development and disease.
• What they did: The authors engineered a Drosophila So missense mutant, So{Delta}Eya (C110S), to abrogate PPI-Eya, then used heterologous leucine zipper domains to selectively reconstitute the So{Delta}Eya-Eya PPI in cultured cells and in vivo.
• The result: The reconstituted complex is transcriptionally active and rescues eye formation, and PPI-Rescue also restores activity to So{Delta}PPI (V111E), modeling the human SIX1(V17E) allele linked to Branchio-Oto-Renal syndrome.

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