Signals, pathways and splicing regulation.

Alternative splicing of messenger RNA precursors is an extraordinary source of protein diversity and the regulation of this process is crucial for diverse cellular functions in both physiological and pathological situations. For many years, several signaling pathways have been implicated in alternative splicing regulation. Recent work has begun to unravel the molecular mechanisms by which extracellular stimuli activate signaling cascades that modulate the activity of the splicing machinery and therefore the splicing pattern of many different target messenger RNA precursors. These experiments are revealing unexpected aspects of the mechanism that control splicing and the consequences of the regulated splicing events. We summarize here the current knowledge about signal-induced alternative splicing regulation of Slo, NR1, CD44, CD45 and fibronectin genes, and also discuss the importance of some of these events in determination of cellular fate. Furthermore, we highlight the relevance of signal-induced changes in phosphorylation state and subcellular distribution of splicing factors as a way of regulating the splicing process. Lastly, we explore new and unexpected findings about regulated splicing in anucleated cells.