We use multidisciplinary approaches to study RNA splicing mechanisms and regulation. A major focus has been the identification and characterization of human proteins involved in the two catalytic steps of splicing or in regulating alternative splicing. We study the detailed structures, posttranslational modifications, RNA-binding, and functions of selected factors, as well as their subcellular localization and mechanisms of action in vivo. In particular, we study the human SR (serine/arginine-rich) and hnRNP (heterogeneous nuclear ribonucleoprotein) A/B protein families. We are interested in their mechanisms of action and their specificity in the recognition of exonic or intronic splicing enhancer and silencer elements, which are important for splice-site selection and splicing efficiency. We recently demonstrated that SF2/ASF is an oncoprotein. We also investigate the mechanisms by which point mutations in exons or introns result in aberrant splicing, leading to numerous genetic diseases. In particular, we have focused on the SMN1/2 genes associated with a motor-neuron disease, spinal muscular atrophy. We have developed specific compounds to suppress exon skipping, for both mechanistic studies and therapeutic applications, and we have already shown splicing correction of human SMN2 in transgenic mice.