Regulations of RNA splicing

The University of Paris-Saclay is looking for a candidate for a thesis on the mechanism of RNA splicing in eukaryotes. The candidate will work in the SABNP laboratory which is dedicated to the study of RNA binding proteins using integrative approaches combining biochemical, structural and functional analyzes (http://sabnp.univ-evry.fr).

Scientific project:

RNA splicing is a key step in genome expression that is often altered in genetic diseases and cancers (1). However, detailed knowledge of the mechanisms enabling precise splice site recognition is still lacking. In this context, our team studies the interactions between the factors involved in splice site recognition (2, 3).

The student will carry out biochemical and functional analyzes to characterize the interactions between several splicing factors. The sequences targeted by these factors will also be sought by in vitro RNA-protein interaction analyzes and tested in vivo. Finally, the role of these interactions in the splicing of target genes will be investigated in cellular models. All the results will make it possible to propose new modes of splicing regulation.

1. Bonnal, S. C., López-Oreja, I., and Valcárcel, J. (2020) Roles and mechanisms of alternative splicing in cancer - implications for care. Nat. Rev. Clin. Oncol. 17, 457–474

2. Tari, M., Manceau, V., de Matha Salone, J., Kobayashi, A., Pastré, D., and Maucuer, A. (2019) U2AF65 assemblies drive sequence-specific splice site recognition. EMBO Rep. 20, e47604

3. Kobayashi, A., Clément, M.-J., Craveur, P., El Hage, K., Salone, J. de M., Bollot, G., Pastré, D., and Maucuer, A. ( 2022) Identification of a small molecule splicing inhibitor targeting UHM domains. FEBS J. 289, 682–698

Host laboratory and context: The successful candidate will be funded by the SDSV doctoral school and will carry out research within the SABNP laboratory (INSERM UMR1204 research unit) at the University of Evry, and part of the Genopole biocluster for biotechnologies.

Contact and application: For more information, please contact Alexandre Maucuer. 

Funding category: Contrat doctoral



PHD title: Doctorat en Biologie

PHD Country: France