Alexandre MAUCUER

alexandre.maucuer(at)inserm.fr

Postdoctoral position open

RNA splicing in nervous system development and disease.

Most genes in higher eukaryotes are initially transcribed as pre-mRNAs from which intervening sequences are removed to yield mature mRNAs, a process known as splicing. Pre-mRNA splicing is a crucial step for correct protein expression. Through the use of different splice sites leading to alternative transcripts, splicing is also a source of an extraordinary molecular diversity and as such plays a key role in gene regulation. In particular in the nervous system alternative splicing is highly prevalent and conserved. Finally, splicing errors are nowadays estimated as the most frequent causative mutations in genetic diseases.

splicing

To understand how disease causing mutations affect splicing and to raise therapies based on restoring splicing, a deep knowledge of splicing mechanisms at the molecular level is mandatory. Our group participated in the functional and structural characterization of 3’ splice site binding factors with a particular focus on U2AF Homology proteins. In addition we identified novel putative splicing regulators through shRNA screening strategies and bioinformatics approaches.

In the team we combine molecular, gene silencing (shRNA/Cripsr), transcriptomics and bioinformatics approaches with the use of models of neuronal cell cultures to address the function of these splicing regulators.dif
Our major focus is now to determine the RNA targets of splicing factors of interest and their mode of action in splicing, mailabellingnly in the developing nervous system. Identification of their sequence targets and comparison of their splicing signature with that associated with genetic diseases should allow an evaluation of the association of these splicing factors with splicing defects in the disease including neurodegenerative disorders.

Publications

Group members:
Alexandre Maucuer. Ph.D., principal investigator, (INSERM)
Jean Salone: Laboratory technician (INSERM)

XY Chang, Postdoc (UEVE)
Manel Tari, Ph.D. student (SDSV)

Teaching:
Parcours « Biochimie et Génétique des ARN »Spécialité Master 2 Biochimie – Paris VI
Cours : « Mécanismes de régulation de l’épissage des ARN pré-messagers »