Project description
Transcription factors and mRNA processing
The combination of transcription factors (TF) and cofactors regulates the transcription process in a precise spatiotemporal manner. The evolutionarily conserved class of Hox TF represents an example of how a restricted number of TF drive diverse transcriptional programmes. The EU-funded RNA-NetHOX project aims to employ model systems to study the impact of Hox-dependent mRNA processing regulation. The research will elucidate how interactions with splicing factors impact Hox functions in vivo in Drosophila embryos. The cooperation between Hox and splicing factors will be further investigated in large-scale interaction screens of several human Hox and 2 000 RNA-regulatory proteins in various normal and pathological cell contexts.
Objective
Cell fate decisions is governed by the fine-tuned regulation of gene expression in all living organism. It is mostly realized by the cell-type specific assembly of regulatory networks consisting of Transcription Factors (TFs) and cofactors proteins. Thus, a multitude of combination between TF and cofactors will be set up to regulate the transcription in a precise spatiotemporal manner. The evolutionary conserved class of Hox TFs perfectly illustrates how a restricted number of TFs is able to promote diverse transcriptional programs. Hox proteins are involved in the specification of body forms and organs in animals. Despite this notorious architectural role, their operating mode remains controversial: they recognize similar DNA-binding sites in vitro, in sharp contrast with their specific functions in vivo. Thus, Hox proteins are likely acting with cofactors in vivo, and their identification was the core of my post-doctoral work. Notably, it revealed that mRNA-processing related proteins could constitute an important class of Hox cofactors. Thus, Hox specificity could also rely on mRNA-processing regulation, providing insightful molecular entry points to understand Hox function in development and disease. My research project aims at elucidating this novel facet of Hox activity. I propose two complementary aims developed in two model systems in order to decipher the molecular and functional impact of Hox-dependent mRNA processing regulation. I will decipher how interactions with splicing factors impact on the Hox functions in vivo in Drosophila embryos. Moreover, I will enlarge the cooperative role of HOX and splicing factors by performing large-scale interaction-screens of several human HOX and 2000 RNA-regulatory proteins in various normal and pathological cell contexts. Overall, my research program has the ambition to open novel perspectives on the role of TFs at the mRNA-regulatory level.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
75794 Paris
France