A Genetic Screen for Dominant Modifiers of a Small-Wing Phenotype in Drosophila melanogaster Identifies Proteins Involved in Splicing and Translation

¹ Cancer Research UK London Research Institute

^* To whom correspondence should be addressed. E-mail: sally.leevers{at}cancer.org.uk.

Submitted on April 29, 2005
Revised on June 8, 2005
Accepted on 24 June 2005

	Abstract

Studies in the fly, Drosophila melanogaster, have revealed that several signalling pathways are important for the regulation of growth. Amongst these, the Insulin receptor/phosphoinositide 3-kinase (PI3K) pathway is remarkable in that it affects growth and final size without disturbing pattern formation. We have used a small-wing phenotype, generated by mis-expression of kinase-dead PI3K, to screen for novel mutations that specifically disrupt organ growth in vivo. We identified several complementation groups that dominantly enhance this small-wing phenotype. Meiotic recombination in conjunction with visible markers and single nucleotide polymorphisms (SNPs) was used to map five enhancers to single genes. Two of these, nucampholin and prp8, encode pre-mRNA splicing factors. The three other enhancers encode factors required for mRNA translation: pixie encodes the Drosophila ortholog of yeast RLI1, and RpL5 and RpL38 encode proteins of the large ribosomal subunit. Interestingly, mutations in several other ribosomal protein-encoding genes also enhance the small-wing phenotype used in the original screen. Our work has therefore identified mutations in five previously uncharacterized Drosophila genes, and provides in vivo evidence that normal organ growth requires optimal regulation of both pre-mRNA splicing and mRNA translation.

Key Words: Drosophila melanogaster, growth screen, mapping, splicing, translation

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