Splicing and the Single Cell

The selection of alternative splice sites is an important component of cell-specific gene regulation in eukaryotic cells. Use of splice sites can be positively and negatively regulated, and often physiologically appropriate splice site choice is achieved by a balance of the two. RNA elements controlling splice site choice are found in both exons and introns, and these determine management by the cellular splicing machinery. However, the molecular basis of how the splicing machinery responds to these signals in different cells is somewhat of a paradox. Thus far the identified proteins which bind to tissue/cell-specific regulatory elements in mammals are expressed in many different tissues, and not just in the regulating tissue. Potential tissue-specific splicing regulators have been identified by non-biochemical means. However, alternative splicing choices are likely to be affected by subtle differences in the splicing machinery in different cells. In this review I suggest that one important factor is the ratio of proteins in different nuclear compartments, which might be established in a cell type specific fashion.