Alternative splicing is an efficient mechanism for the generation of protein diversity: contractile protein genes as a model system

Abstract

Alternative splicing has emerged in recent years as a widespread device for regulating gene expression and generating protein diversity. Its analysis has provided some mechanistic understanding of this form of gene regulation and, in addition, has provided new insights into some fundamental aspects of splicing. This mode of regulation is particularly prevalent in muscle cells, where genes such as troponin T are able to generate up to 64 different isoforms from a single transcriptional unit. Alternative splicing has the potential to raise the coding capacity of the small multigene families that code for the contractile proteins so that several million structurally different sarcomeres can be generated. The mammalian alpha-tropomyosin gene has proved particularly useful for the analysis of the mechanisms involved in this type of regulation. In particular, the mutually exclusive splicing of exons 2 and 3 has provided answers about the processes involved in the three main regulatory steps: (a) establishment of mutually exclusive behavior; (b) the elements involved in setting up the default pattern of splicing, and (c) the switch from the default to the regulated splicing pattern in some cell types.