Eukaryotic gene expression is regulated in a combinatorial manner and on several interconnected layers, ranging from epigenetic mechanisms, transcription, RNA processing to protein stages. mRNA processing plays a major role in tissue- and development-dependent regulation, in particular alternative pre-mRNA splicing, which greatly enhances the capacity and composition of the proteome. Within the last decade, novel methods have been developed to systematically study the complex networks between regulatory alternative splicing factors and their RNA targets. This minireview focuses on cross-linking and immunoprecipitation methods, which - in combination with deep RNA sequencing - have made an important contribution in unraveling these networks.