Molecular interactions during early spliceosome assembly in normal and disease cells.
Most genes in higher eukaryotes are initially transcribed as pre-mRNAs from which intervening sequences are removed. This pre-mRNA splicing is a crucial step for correct protein expression. In addition, the use of different splice sites is a source of an extraordinary molecular diversity and plays a key role in gene regulation. Finally, this precision mechanism is affected in cancer and genetic diseases.
To understand how disease causing mutations affect splicing and to raise therapies based on restoring splicing, a deep knowledge of splicing mechanisms is mandatory. Our work is dedicated at the functional and structural characterization of 3’ splice site binding factors with a particular focus on proteins presenting a U2AF Homology Motif that participate in a network of interactions for splice site recognition (eg. U2AF65, CAPERa, SPF45 and PUF60).
First steps in spliceosome assembly
In the team, we combine molecular, structural, gene silencing, transcriptomics, and bioinformatics approaches to address the functions and regulations of splicing factors. Our major focus is to determine their RNA targets and their action in splice site recognition.
Searching for their target sequences and comparing with splicing defects in diseases should open new avenues to try restoring splicing in cancer, neurodevelopmental syndromes, and neurodegenerative disorders.
Alexandre Maucuer. Ph.D., principal investigator, (INSERM)
Jean Salone: Laboratory technician (INSERM)
Hsiang-Yu Chang, Postdoc (UEVE)
Manel Tari, Ph.D. student (SDSV)
Asaki Kobayashi, Ph.D. student (SDSV)