"Cancer diseases affect millions of people worldwide and are a source of great burden to society, both financially and in terms of health care resources. In Europe, Every day 5.214 Europeans are diagnosed with cancer and 3.185 die from their disease (20% of total cases are related to lung cancer). Understanding of how genetic factors contribute to these diseases is gathering speed. Genome-wide association analyses on large patient cohorts are generating large sets of candidate genes. A frequent genetic alteration observed in heavy smokers, lung cancer and other tissue carcinomas is the deletion of chromosomal region 3p21.3 where the LUCA15/RBM5 (RNA binding Motif 5) gene maps. RBM5 protein levels are misregulated in several cancers such as lung and breast cancers and constitute one molecular signature associated with metastasis in various solid tumors. RBM5 is an RNA binding protein harboring several domains involved in RNA metabolism and pre-mRNA splicing. Recent data revealed that RBM5 binds to a U/C-rich sequence in the caspase-2 pre-mRNA and that it regulates the alternative splicing of apoptosis-related genes such as the “death receptor” Fas (CD95/APO-1) and its key inhibitor c-FLIP pre-mRNAs. The goal of this proposal is to identify and characterize of RBM5 containing complexes. We will use the Cross Link ImmunoPrecipitation (CLIP) technique coupled to deep sequencing to identify RBM5 RNA targets and to draw a functional map correlating their positions with the alternative splicing event of their targets. To identify RBM5 protein partners, we will use gel chromatography to purify RBM5 containing complex(es) and MALDI-TOFF to identify RBM5 interactors in these complex(es). This information will help us to analyze the regulation of c-FLIP pre-mRNA splicing by RBM5. Hopefully, the results will allow us the design of new potential therapeutic strategies aimed to inhibiting the massive cell transformation occurring during the tumor progression processes."