Abstract:

The architecture of mammalian genes enables the production of multiple transcripts that greatly expand the coding capacity of our genomes. Understanding how these transcripts are regulated is of particular importance in cancer genomics, as their aberrant regulation contributes to the ~10 million cancer-related deaths each year. We recently described a phenomenon called exon-mediated activation of transcription starts (EMATS) in which the splicing of internal exons impacts the spectrum of promoters used and expression level of the host gene. We showed that targeted-inhibition of splicing reduces the usage of promoters and suppresses gene expression, while evolutionary creation of a new splice site can activate cryptic promoters. My findings support a model in which splicing factors recruit transcription machinery to influence promoter choice and regulate the expression of thousands of mammalian genes.