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Regulated alternative polyadenylation is an important feature of gene expression, but how gene transcription rate affects this process remains to be investigated. polo is a cell-cycle gene that uses two poly(A) signals in the 3' untranslated region (UTR) to produce alternative messenger RNAs that differ in their 3'UTR length. Using a mutant Drosophila strain that has a lower transcriptional elongation rate, we show that transcription kinetics can determine alternative poly(A) site selection. The physiological consequences of incorrect polo poly(A) site choice are of vital importance; transgenic flies lacking the distal poly(A) signal cannot produce the longer transcript and die at the pupa stage due to a failure in the proliferation of the precursor cells of the abdomen, the histoblasts. This is due to the low translation efficiency of the shorter transcript produced by proximal poly(A) site usage. Our results show that correct polo poly(A) site selection functions to provide the correct levels of protein expression necessary for histoblast proliferation, and that the kinetics of RNA polymerase II have an important role in the mechanism of alternative polyadenylation.

Original publication

DOI

10.1038/emboj.2011.156

Type

Journal article

Journal

EMBO J

Publication Date

20/05/2011

Volume

30

Pages

2431 - 2444

Keywords

3' Untranslated Regions, Animals, Animals, Genetically Modified, Cell Proliferation, Cell Survival, Drosophila Proteins, Drosophila melanogaster, Genetic Variation, Kinetics, Poly A, Polyadenylation, Protein-Serine-Threonine Kinases, RNA Polymerase II, Signal Transduction