UC Santa Cruz

Key PointsRNA-binding proteins (RBPs) have a major role in creating cell-type-specific regulation of alternative splicing, but our ability to predict their action on the basis of genomic sequence remains primitive.RBPs recognize similar RNA sequence motifs as either splicing enhancers or splicing silencers depending on position, which indicates that sequence context is important for regulation.The context of splicing regulatory sequences is determined both by the nature of nearby pre-mRNA sequences and by the array of other RBPs expressed in the cell, and it remains poorly defined.Biochemical and molecular studies have revealed combinatorial behaviour of specific splicing factors at specific genes, but these examples represent a small proportion of the context-dependent RBP activity across the transcriptome.Several unrelated RBPs follow a common set of rules for position-specific activities, which suggests that they share common mechanisms for controlling the splicing apparatus.A complete inventory of RBPs and the sequences they recognize, as well as their expression profiles and a mechanistic understanding of splicing regulation, will be necessary before we can understand how the genomic sequence leads to alternative splicing regulation.