Not Quite the Same: How Alternative Splicing Affects Protein Interactions

Alternative splicing is a regulatory mechanism in eukaryotic organisms that allows for production of different protein isoforms from the same gene. These isoforms differ in sequence and often in structure. Recently, it has been shown that they also differ in their capacity to interact with other proteins. However, in publicly available protein–protein interaction resources, isoforms are mostly neglected, resulting in both false-positive and false-negative interactions. We first describe the role of alternative splicing for protein–protein interactions and explain the challenges of obtaining isoform-based interaction networks. We present a list of computational approaches that could be used to investigate the effect of alternative splicing on individual proteins and protein–protein interactions. Finally, we suggest future work and research directions.