A genetic screen for dominant modifiers of a small-wing phenotype in Drosophila melanogaster identifies proteins involved in splicing and translation.
Studies in the fly, Drosophila melanogaster, have revealed that several signaling pathways are important for the regulation of growth. Among 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 misexpression 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.
Growth Regulation Laboratory, Cancer Research UK London Research Institute.
Carmen M A
CM
Coelho
Benjamin
B
Kolevski
Cherryl D
CD
Walker
Irene
I
Lavagi
Thomas
T
Shaw
Anselm
A
Ebert
Sally J
SJ
Leevers
Steven J
SJ
Marygold
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D040461:Gene Components; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D014176:Protein Biosynthesis / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D014921:Wings, Animal / Q000254:growth & development*
D029721:Drosophila Proteins