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PMID: 7479058 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Aberrant pre-mRNA maturation is caused by LINE insertions into introns of the white gene of Drosophila melanogaster.

Nucleic acids research ·Vol. 23 ·No. 20 ·1995-10-25 ·Pages 4015-22

Lajoinie O, Drake ME, Dastugue B, Vaury C

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
ATP-Binding Cassette Transporters Alleles Amino Acid Sequence Animals Base Sequence DNA Transposable Elements Drosophila Proteins Drosophila melanogaster/genetics Eye Proteins Gene Expression Regulation, Developmental Genes, Insect/genetics Insect Hormones/genetics Introns/genetics Molecular Sequence Data Mutagenesis, Insertional/genetics Organ Specificity RNA Precursors/genetics RNA Splicing/genetics RNA, Messenger/analysis
Chemicals
ATP-Binding Cassette Transporters DNA Transposable Elements Drosophila Proteins Eye Proteins Insect Hormones RNA Precursors RNA, Messenger w protein, Drosophila
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lajoinie O
INSERM U384, Faculté de Médecine, Clermont-Ferrand, France.
Drake M E
Dastugue B
Vaury C
References (54)
54 references, click to expand
  1. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
    Science. 1994 Sep 16;265(5179):1706-9 PMID: 8085156
  2. Structure and transcription of the Drosophila melanogaster vermilion gene and several mutant alleles.
    Mol Cell Biol. 1990 Apr;10(4):1423-31 PMID: 2108317
  3. A reappraisal of non-consensus mRNA splice sites.
    Nucleic Acids Res. 1991 Jul 25;19(14):3795-8 PMID: 1713664
  4. A detailed developmental and structural study of the transcriptional effects of insertion of the Copia transposon into the white locus of Drosophila melanogaster.
    Genetics. 1985 Nov;111(3):495-515 PMID: 2414153
  5. AU-rich intronic elements affect pre-mRNA 5' splice site selection in Drosophila melanogaster.
    Mol Cell Biol. 1993 Dec;13(12):7689-97 PMID: 8246985
  6. Interaction between the first and last nucleotides of pre-mRNA introns is a determinant of 3' splice site selection in S. cerevisiae.
    Nucleic Acids Res. 1994 Jun 11;22(11):1981-7 PMID: 8029003
  7. Splicing signals in Drosophila: intron size, information content, and consensus sequences.
    Nucleic Acids Res. 1992 Aug 25;20(16):4255-62 PMID: 1508718
  8. An indicator gene for detection of germline retrotransposition in transgenic Drosophila demonstrates RNA-mediated transposition of the LINE I element.
    EMBO J. 1991 Jul;10(7):1927-37 PMID: 1710982
  9. Effect of 5' splice site mutations on splicing of the preceding intron.
    Mol Cell Biol. 1990 Dec;10(12):6299-305 PMID: 2247057
  10. Puffs and PCR: the in vivo dynamics of early gene expression during ecdysone responses in Drosophila.
    Development. 1993 Jun;118(2):613-27 PMID: 8223281
  11. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.
    Nature. 1988 Mar 10;332(6160):164-6 PMID: 2831458
  12. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.
    Cancer Res. 1992 Feb 1;52(3):643-5 PMID: 1310068
  13. Mutually exclusive splicing of alpha-tropomyosin exons enforced by an unusual lariat branch point location: implications for constitutive splicing.
    Cell. 1989 Mar 10;56(5):749-58 PMID: 2924347
  14. I transposable elements and I-R hybrid dysgenesis in Drosophila.
    Trends Genet. 1990 Jan;6(1):16-21 PMID: 2158161
  15. Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy.
    J Clin Invest. 1993 May;91(5):1862-7 PMID: 8387534
  16. Exon recognition in vertebrate splicing.
    J Biol Chem. 1995 Feb 10;270(6):2411-4 PMID: 7852296
  17. Evidence for retrotransposition of the I factor, a LINE element of Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4907-10 PMID: 1647020
  18. Molecular lesions associated with white gene mutations induced by I-R hybrid dysgenesis in Drosophila melanogaster.
    EMBO J. 1984 Dec 20;3(13):3079-85 PMID: 16453589
  19. DNA sequence of the white locus of Drosophila melanogaster.
    J Mol Biol. 1984 Dec 15;180(3):437-55 PMID: 6084717
  20. Interaction of the mottler of white with transposable element alleles at the white locus in Drosophila melanogaster.
    Genes Dev. 1989 Jan;3(1):73-84 PMID: 2540060
  21. Developmental expression of the white locus of Drosophila melanogaster.
    EMBO J. 1984 Sep;3(9):2087-94 PMID: 16453550
  22. Transposable elements controlling I-R hybrid dysgenesis in D. melanogaster are similar to mammalian LINEs.
    Cell. 1986 Dec 26;47(6):1007-15 PMID: 2430722
  23. Mobile element insertions causing mutations in the Drosophila suppressor of sable locus occur in DNase I hypersensitive subregions of 5'-transcribed nontranslated sequences.
    Genetics. 1990 Dec;126(4):1071-82 PMID: 1963868
  24. Analysis of spliceosome assembly and the structure of a regulated intron in Drosophila in vitro splicing extracts.
    Nucleic Acids Res. 1992 Nov 11;20(21):5719-27 PMID: 1333586
  25. Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project.
    Methods Enzymol. 1990;183:252-78 PMID: 2314278
  26. I elements of Drosophila melanogaster generate specific chromosomal rearrangements during transposition.
    Mol Gen Genet. 1989 Aug;218(2):222-8 PMID: 2550769
  27. The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA-binding protein.
    Genes Dev. 1988 Oct;2(10):1205-15 PMID: 2462523
  28. The determined state of white expression in the Drosophila eye is modified by zeste1 in the wzm family of mutants.
    Mol Gen Genet. 1994 Mar;242(6):717-26 PMID: 8152422
  29. Evidence that a regulatory gene autoregulates splicing of its transcript.
    EMBO J. 1987 Dec 20;6(13):4105-11 PMID: 3443103
  30. A sequence compilation and comparison of exons that are alternatively spliced in neurons.
    Nucleic Acids Res. 1994 May 11;22(9):1515-26 PMID: 8202349
  31. LINE-1: a mammalian transposable element.
    Biochim Biophys Acta. 1987 Dec 8;910(3):203-12 PMID: 2445384
  32. Branch point selection in alternative splicing of tropomyosin pre-mRNAs.
    Nucleic Acids Res. 1989 Jul 25;17(14):5633-50 PMID: 2762151
  33. Information content of Caenorhabditis elegans splice site sequences varies with intron length.
    Nucleic Acids Res. 1990 Mar 25;18(6):1509-12 PMID: 2326191
  34. Polypurine sequences within a downstream exon function as a splicing enhancer.
    Mol Cell Biol. 1994 Feb;14(2):1347-54 PMID: 8289812
  35. Active LINE-1 retrotransposons in human testicular cancer.
    Oncogene. 1992 Mar;7(3):507-10 PMID: 1312702
  36. Aberrant splicing and transcription termination caused by P element insertion into the intron of a Drosophila gene.
    Genetics. 1995 Jan;139(1):327-35 PMID: 7705633
  37. Transcription of the Drosophila white locus and some of its mutants.
    EMBO J. 1984 Mar;3(3):563-8 PMID: 6425054
  38. Exon definition may facilitate splice site selection in RNAs with multiple exons.
    Mol Cell Biol. 1990 Jan;10(1):84-94 PMID: 2136768
  39. Partial revertants of the transposable element-associated suppressible allele white-apricot in Drosophila melanogaster: structures and responsiveness to genetic modifiers.
    Genetics. 1988 Feb;118(2):221-34 PMID: 2834265
  40. Transposing without ends: the non-LTR retrotransposable elements.
    New Biol. 1992 May;4(5):430-40 PMID: 1325183
  41. Actin gene expression is modulated by ecdysterone in a Drosophila cell line.
    J Mol Biol. 1983 Mar 5;164(3):419-30 PMID: 6302276
  42. A long interspersed repetitive element--the I factor of Drosophila teissieri--is able to transpose in different Drosophila species.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8887-91 PMID: 2554335
  43. A retrotransposon 412 insertion within an exon of the Drosophila melanogaster vermilion gene is spliced from the precursor RNA.
    Genes Dev. 1990 Apr;4(4):559-66 PMID: 2163342
  44. Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome.
    Cell. 1983 Aug;34(1):25-35 PMID: 6309410
  45. Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma.
    Nature. 1988 May 5;333(6168):87-90 PMID: 2834650
  46. I-R hybrid dysgenesis in Drosophila melanogaster: nature and site specificity of induced recessive lethals.
    Mutat Res. 1990 Jun;230(2):135-57 PMID: 2115618
  47. A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding.
    Genes Dev. 1993 Dec;7(12A):2405-17 PMID: 8253386
  48. Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro.
    Cell. 1992 May 29;69(5):795-807 PMID: 1591778
  49. Effects of transposable element insertions on RNA encoded by the white gene of Drosophila.
    Cell. 1984 Sep;38(2):471-81 PMID: 6088083
  50. Drosophila melanogaster mutations suppressible by the suppressor of Hairy-wing are insertions of a 7.3-kilobase mobile element.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1678-82 PMID: 6300868
  51. Transcription of the white locus in Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 1983 Nov;80(22):6917-21 PMID: 16593390
  52. Identification of a potential RNA intermediate for transposition of the LINE-like element I factor in Drosophila melanogaster.
    EMBO J. 1990 Nov;9(11):3557-63 PMID: 1698618
  53. The I--R system of hybrid dysgenesis in Drosophila melanogaster: are I factor insertions responsible for the mutator effect of the I--R interaction?
    Mol Gen Genet. 1981;183(1):123-9 PMID: 6276672
  54. Synergistic interactions between two distinct elements of a regulated splicing enhancer.
    Genes Dev. 1995 Feb 1;9(3):284-93 PMID: 7867927
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1995-10-25
Pages
4015-22
Language
English
Region
England
NLM ID
0411011
PMCID
PMC307336
Subset
IM
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