Signal transduction and post-transcriptional gene expression

Traditionally, growth factor-coupled signaling to the nucleus has been thought to be primarily directed toward transcriptional regulation. However, there are now increasing indications from a diversity of experimental systems that other aspects of RNA processing, including translation, lifetime and stability, and splicing are under strict growth factor control. In this review, we present the emerging evidence for growth factor signaling pathways that impact on these different RNA processing events. Particularly noteworthy is the realization that growth factor signaling through Ras can effect the regulation of two RNA cap-binding proteins, the cytosolic eIF-4E complex, which is necessary for initiating translation, and the nuclear cap-binding complex, the CBC, which plays a role in cap-dependent pre-mRNA splicing, U snRNA export and 3'-end processing. This, taken together with other findings that demonstrate the ability of stress response pathways and the small G protein, Cdc42, to activate the CBC, raises some interesting possibilities regarding how signaling to the two cellular RNA cap-binding protein complexes may coordinate the growth-coupled regulation of gene expression at the level of RNA processing.