title: Aberrant pre-mRNA maturation is caused by LINE insertions into introns of the white gene of Drosophila melanogaster.
abstract: Insertional mutagenesis screens have provided thousands of mutant alleles for analysing genes of varied functions in Drosophila melanogaster. We here document mechanisms of insertional mutagenesis by a LINE element, the I factor, by determining the molecular structure of RNAs produced from two alleles of the white gene of D.melanogaster, wIR1 and wIR6. These alleles result from insertion of the I factor into introns of the gene. We show that sequences present within the element direct aberrant splicing and termination events. When the I factor is inserted within the white first intron it may lead to the use of a cryptic 3' splice site which does not contain the dinucleotide AG. This splicing gives rise to a chimeric messenger RNA whose synthesis is controlled differently in tissues where the mutated gene is expressed. When the I factor is inserted within the white last intron it induces synthesis of truncated mRNAs. These results provide, for the first time, mechanisms for I factor insertional mutagenesis. They are discussed in the more general context of RNA processing in Drosophila and the evolution of eukaryotic gene introns.
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect / Q000235:genetics; D007301:Insect Hormones / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D009928:Organ Specificity; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D018528:ATP-Binding Cassette Transporters; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D005136:Eye Proteins; D007301:Insect Hormones; D012322:RNA Precursors; D012333:RNA, Messenger; C059254:w protein, Drosophila