Seminar

Networks of alternative splicing regulation in cancer

Prof. Juan Valcárcel

Alternative splicing of messenger RNA precursors is a key step in the regulation of gene expression in eukaryotes, contributing to proteome diversity and functional control of many biological processes. Alterations in alternative splicing contribute to every cancer hallmark, from metabolic reprogramming to therapy resistance or metastasis. The machinery in charge of intron removal, the spliceosome, is composed of 5 small nuclear Ribonucleoprotein complexes and over 150 proteins. Unexpectedly, core components of the spliceosome, believed to be essential for intron removal in general, are frequently mutated in cancer and are the targets of anti-tumor drugs. I will discuss our efforts to understand molecular mechanisms of splice site selection by core splicing factors and their implications for the design of novel cancer therapies.