The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2022

The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II

Panagiotis Boumpas
  • Fonction : Auteur
Patrick van Nierop y Sanchez
  • Fonction : Auteur
Katrin Domsch
  • Fonction : Auteur
Hugo Daniel Pinto
  • Fonction : Auteur
Pedro Borges Pinto
  • Fonction : Auteur
Ingrid Lohmann
  • Fonction : Auteur

Résumé

Abstract Transcription factors (TFs) play a pivotal role in cell fate decision by coordinating gene expression programs. Although most TFs act at the DNA layer, few TFs bind RNA and modulate splicing. Yet, the mechanistic cues underlying TFs activity in splicing remain elusive. Focusing on the Drosophila Hox TF Ultrabithorax (Ubx), our work shed light on a novel layer of Ubx function at the RNA level. Transcriptome and genome-wide binding profiles in embryonic mesoderm and Drosophila cells indicate that Ubx regulates mRNA expression and splicing to promote distinct outcomes in defined cellular contexts. Our results demonstrate a new RNA-binding ability of Ubx. We find that the N51 amino acid of the DNA-binding Homeodomain is non-essential for RNA interaction in vitro, but is required for RNA interaction in vivo and Ubx splicing activity. Moreover, mutation of the N51 amino acid weakens the interaction between Ubx and active RNA Polymerase II (Pol II). Our results reveal that Ubx regulates elongation-coupled splicing, which could be coordinated by a dynamic interplay with active Pol II on chromatin. Overall, our work uncovered a novel role of the Hox TFs at the mRNA regulatory layer. This could be an essential function for other classes of TFs to control cell diversity.
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Dates et versions

hal-04242158 , version 1 (18-10-2023)

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Julie Carnesecchi, Panagiotis Boumpas, Patrick van Nierop y Sanchez, Katrin Domsch, Hugo Daniel Pinto, et al.. The Hox transcription factor Ultrabithorax binds RNA and regulates co-transcriptional splicing through an interplay with RNA polymerase II. Nucleic Acids Research, 2022, 50 (2), pp.763-783. ⟨10.1093/nar/gkab1250⟩. ⟨hal-04242158⟩
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