Intron Removal, Alternative Splicing, and Genomics Manuel Ares, Jr., MCD Biology Our work centers on the mechanisms and regulation of splicing. Splicing is required to remove intron sequences from pre-mRNA and create coding sequences for translation. We study yeast, mouse and human tissues and cells, which share many fundamental features but also have distinct and important differences from each other. We are generally interested in the structure and function of RNAs that play important regulatory and catalytic roles. We use experiments to try to understand (1) the mechanism of action of the core components of the spliceosome, in particular the snRNAs and their rearrangements during assembly of the spliceosome and catalysis of the splicing reactions (2) the regulation of alternative splicing at a mechanistic level including the coupling of splicing to transcription and RNA decay mechanisms, and (3) the coordinate regulation of splicing events in developing systems. We design and print our own microarrays that measure splicing and alternative splicing, and are using them to determine the effects of mutations or other perturbations on broad sets of splicing events. Our goal is to develop an integrated and comprehensive understanding of the role of splicing in specific processes and biological events, inparticular for genes whose function and regulation at the level of splicing may be difficult to discern by traditional methods.