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Highlights Ubx homodimerization enables decoupling of DNA- and RNA-dependent splicing regulation The homeodomain K58 amino acid is critical for Ubx-RNA binding ability Ubx-RNA binding ability is essential for splicing regulation Dual DNA/RNA binding activities shape Ubx homeotic functions INTRODUCTION Transcription factors (TFs) play a critical role in coordinating the development of multicellular organisms by regulating precise gene expression programs 1,2

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