title: The Drosophila melanogaster multidrug-resistance protein 1 (MRP1) homolog has a novel gene structure containing two variable internal exons.
abstract: Drosophila melanogaster has a gene very similar to human MRP1 that encodes a full ABC-transporter containing three membrane-spanning domains and two nucleotide-binding domains. This 19 exon insect gene, dMRP (FBgn0032456), spans slightly more than 22 kb. The cDNA SD07655 representing this gene was sequenced and found to contain sequences from 12 exons including single copies of two exons having multiple genomic copies. The gene contains two variant copies of exon 4 and seven of exon 8. While a cDNA contains only one version of each variable exon, all forms of these variable exons were detected in adult fly mRNA. These results predict that Drosophila could make 14 different MRP isoforms from a single gene by substituting different variable exons. This is the first report of any organism using differential splicing of alternative, internal exons, to produce such a large array of MRP isoforms having the same size, but with limited and defined internal variations. Defining the functional differences in the dMRP isoforms should provide clues to the structure/function relationships of the amino acids in these MRP domains, both for the insect enzyme and for those of other species.
authors.affiliation: Institut Pasteur, Unité de Biochimie et Biologie Moléculaire des Insectes, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Grailles
authors.forename: Paul T
authors.initials: PT
authors.lastname: Brey
authors.forename: Charles W
authors.initials: CW
authors.lastname: Roth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D015870:Gene Expression; D017344:Genes, Insect / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D004247:DNA; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1