TLS, EWS and TAF15: a model for transcriptional integration of gene expression.

Multifunctional proteins are demonstrating that gene expression is not a series of compartmentalized events beginning with transcription and culminating in delivery of mature mRNA into the cytoplasm, but an integrated pathway of transcription, splicing, RNA metabolism and subcellular targeting of translation. One such multifunctional family is made up of the RNA-binding proteins TLS, EWS and TAF15. These three proteins each contribute a potent transcriptional activation domain to oncogenic fusion proteins, and the formation of these fusion genes are thought to be the primary causes of their associated cancers. Wild-type TLS, EWS and TAF15 can function as classical transcription factors in addition to their better-known functions in splicing and mRNA transport. The interaction between TLS and the stress-response protein YB-1 is an example of how these proteins can induce a multi-faceted change in gene expression, as they can interact to induce changes in both transcription and splicing of target genes. Investigating the multiple functions of TLS, EWS and TAF15 will enhance our understanding of gene expression as a whole, and also allow us to better understand how these proteins may be contributing to the oncogenic pathways the associated fusion proteins initiate.