Nucleic Acids Research, 2003, Vol. 31, No. 14 3873-3880
© 2003 Oxford University Press
A Hox gene mutation that triggers nonsense-mediated RNA decay and affects alternative splicing during Drosophila development
Laboratory for Development and Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK
*To whom correspondence should be addressed. Tel: +44 1223 331773; Fax: +44 1223 336679; Email: cra21{at}hermes.cam.ac.uk
Nonsense mutations are usually assumed to affect protein function by generating truncated protein products. Nonetheless, it is now clear that these mutations affect not just protein synthesis but also messenger RNA stability. The surveillance mechanism responsible for the detection and degradation of ‘nonsense’ RNA messages is termed nonsense-mediated RNA decay (NMD). Essential biochemical components of the NMD machinery have been defined in several species. Here we identify the Drosophila orthologue of one of these factors, Upf1, and document its expression during embryogenesis. To test whether NMD acts during Drosophila development, we make use of a mutation that introduces a stop codon into a variably spliced exon of the Hox gene Ultrabithorax (Ubx). Using real-time quantitative RT-PCR we demonstrate that Ubx transcripts containing the premature stop codon are expressed at lower levels than their wild type counterpart. Unexpectedly, we also find that the same mutation significantly increases the levels of a Ubx splicing isoform that lacks the exon containing the premature termination codon. These findings indicate that NMD is operational during Drosophila development and suggest that nonsense mutations may affect development by altering the spectrum of splicing products formed, as well as by reducing or eliminating protein synthesis.
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