Molecular Interactions Governing Spliceosome Assembly and the Regulation of Alternative 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).

RNA splicing is a key step in genome expression, often impaired in genetic diseases and cancers. However, detailed knowledge of the mechanisms allowing the recognition of splice sites and the assembly of the splicing machinery, the spliceosome, on target introns is still lacking.

The assembly of the spliceosome on introns involves a complex network of molecular interactions. In this network, the splicing factor U2AF2 (U2 Small Nuclear RNA Auxiliary Factor 2 or U2AF65) plays a central role by binding to a polypyrimidine sequence upstream of the 3' splice site and by allowing the recruitment of the U2snRNP factor on the branchpoint sequence. Interestingly, several driver mutations in cancer have been identified in proteins that interact with U2AF2 during spliceosome assembly: SF3b1, U2AF1 and SRSF2. This suggests that U2AF2 partners have a particular role in splicing deregulation associated with cancers.

In this context, we have recently identified a set of novel proteins interacting in vivo with U2AF2 and whose deregulation could also be involved in cancers.

Based on our preliminary results, the thesis project will aim to research the implication of these proteins in cancers by data mining and to characterize their biochemical and functional interaction with U2AF2.

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.

We are looking for candidates who hold (or are in the process of acquiring) a master's degree (or equivalent) in biochemistry, molecular biology or any field of life sciences. Successful candidates must have good organizational skills and be able to work in a team.