Integrating transcription kinetics with alternative polyadenylation and cell cycle control

Alternative polyadenylation has an important function in regulating gene expression, as accumulating evidence has shown that it is related to many different biological programs such as differentiation, development and even flowering. Recently we have shown using the model organism D. melanogaster, how RNA polymerase II kinetics affects alternative polyadenylation. In six genes, which contain tandem poly(A) signals in the 3'UTR, including the cell cycle gene polo, the proximal poly(A) signal is more efficiently used in flies where a mutation in RNA polymerase II reduces its elongation rate. This finding supports the kinetic coupling model for transcription and alternative polyadenylation. polo is a key cell cycle gene encoding a protein kinase with multiple functions in cell division. To understand the physiological function of polo alternative polyadenylation, transgenic flies were constructed where the distal poly(A) signal was deleted. These individuals still produce the shorter polo mRNA, however they die with severe abdominal abnormalities. Lack of the distal poly(A) signal causes a significant decrease in Polo protein levels, which the histoblasts, the precursor cells of the abdomen, require to divide and proliferate at the onset of metamorphosis. Failure in histoblast proliferation impedes the correct development of the abdominal epidermis, causing lethality at the pupa/metamorphosis developmental stage. Polo protein was also shown to be autoregulated by alternative poly(A) site selection in a feedback loop mechanism. Our work is reviewed here and a model for integrating RNA polymerase II kinetics with alternative polyadenylation and cell cycle control is proposed.