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. 2002 Apr;160(4):1481–1487. doi: 10.1093/genetics/160.4.1481

Trans-splicing as a novel mechanism to explain interallelic complementation in Drosophila.

Fabien Mongelard 1, Mariano Labrador 1, Ellen M Baxter 1, Tatiana I Gerasimova 1, Victor G Corces 1
PMCID: PMC1462063  PMID: 11973303

Abstract

Two mutant alleles of the same gene, each located in one of the two homologous chromosomes, may in some instances restore the wild-type function of the gene. This is the case with certain combinations of mutant alleles in the mod(mdg4) gene. This gene encodes several different proteins, including Mod(mdg4)2.2, a component of the gypsy insulator. This protein is encoded by two separate transcription units that can be combined in a trans-splicing reaction to form the mature Mod(mdg4)2.2-encoding RNA. Molecular characterization of complementing alleles shows that they affect the two different transcription units. Flies homozygous for each allele are missing the Mod(mdg4)2.2 protein, whereas wild-type trans-heterozygotes are able to synthesize almost normal levels of the Mod(mdg4)2.2 product. This protein is functional as judged by its ability to form a functional insulator complex. The results suggest that the interallelic complementation in the mod(mdg4) gene is a consequence of trans-splicing between two different mutant transcripts. A conclusion from this observation is that the trans-splicing reaction that takes place between transcripts produced on two different mutant chromosomes ensures wild-type levels of functional protein.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell A. C., West A. G., Felsenfeld G. Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science. 2001 Jan 19;291(5503):447–450. doi: 10.1126/science.291.5503.447. [DOI] [PubMed] [Google Scholar]
  2. Burge C., Karlin S. Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997 Apr 25;268(1):78–94. doi: 10.1006/jmbi.1997.0951. [DOI] [PubMed] [Google Scholar]
  3. Büchner K., Roth P., Schotta G., Krauss V., Saumweber H., Reuter G., Dorn R. Genetic and molecular complexity of the position effect variegation modifier mod(mdg4) in Drosophila. Genetics. 2000 May;155(1):141–157. doi: 10.1093/genetics/155.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Csink A. K., Henikoff S. Large-scale chromosomal movements during interphase progression in Drosophila. J Cell Biol. 1998 Oct 5;143(1):13–22. doi: 10.1083/jcb.143.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davison D., Chapman C. H., Wedeen C., Bingham P. M. Genetic and physical studies of a portion of the white locus participating in transcriptional regulation and in synapsis-dependent interactions in Drosophila adult tissues. Genetics. 1985 Jul;110(3):479–494. doi: 10.1093/genetics/110.3.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dorn R., Krauss V., Reuter G., Saumweber H. The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11376–11380. doi: 10.1073/pnas.90.23.11376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dorn R., Reuter G., Loewendorf A. Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus in Drosophila. Proc Natl Acad Sci U S A. 2001 Aug 7;98(17):9724–9729. doi: 10.1073/pnas.151268698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fink G. R. A cluster of genes controlling three enzymes in histidine biosynthesis in Saccharomyces cerevisiae. Genetics. 1966 Mar;53(3):445–459. doi: 10.1093/genetics/53.3.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GAREN A., GAREN S. Complementation in vivo between structural mutants of alkaline phosphatase from E. coli. J Mol Biol. 1963 Jul;7:13–22. doi: 10.1016/s0022-2836(63)80015-7. [DOI] [PubMed] [Google Scholar]
  10. Gerasimova T. I., Corces V. G. Chromatin insulators and boundaries: effects on transcription and nuclear organization. Annu Rev Genet. 2001;35:193–208. doi: 10.1146/annurev.genet.35.102401.090349. [DOI] [PubMed] [Google Scholar]
  11. Gerasimova T. I., Gdula D. A., Gerasimov D. V., Simonova O., Corces V. G. A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation. Cell. 1995 Aug 25;82(4):587–597. doi: 10.1016/0092-8674(95)90031-4. [DOI] [PubMed] [Google Scholar]
  12. Geyer P. K., Green M. M., Corces V. G. Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. EMBO J. 1990 Jul;9(7):2247–2256. doi: 10.1002/j.1460-2075.1990.tb07395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ghosh D., Gerasimova T. I., Corces V. G. Interactions between the Su(Hw) and Mod(mdg4) proteins required for gypsy insulator function. EMBO J. 2001 May 15;20(10):2518–2527. doi: 10.1093/emboj/20.10.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harrison D. A., Gdula D. A., Coyne R. S., Corces V. G. A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function. Genes Dev. 1993 Oct;7(10):1966–1978. doi: 10.1101/gad.7.10.1966. [DOI] [PubMed] [Google Scholar]
  15. Hiraoka Y., Dernburg A. F., Parmelee S. J., Rykowski M. C., Agard D. A., Sedat J. W. The onset of homologous chromosome pairing during Drosophila melanogaster embryogenesis. J Cell Biol. 1993 Feb;120(3):591–600. doi: 10.1083/jcb.120.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirose Y., Manley J. L. RNA polymerase II and the integration of nuclear events. Genes Dev. 2000 Jun 15;14(12):1415–1429. [PubMed] [Google Scholar]
  17. Ito K., Awano W., Suzuki K., Hiromi Y., Yamamoto D. The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. Development. 1997 Feb;124(4):761–771. doi: 10.1242/dev.124.4.761. [DOI] [PubMed] [Google Scholar]
  18. Jacobson R. H., Zhang X. J., DuBose R. F., Matthews B. W. Three-dimensional structure of beta-galactosidase from E. coli. Nature. 1994 Jun 30;369(6483):761–766. doi: 10.1038/369761a0. [DOI] [PubMed] [Google Scholar]
  19. Juers D. H., Jacobson R. H., Wigley D., Zhang X. J., Huber R. E., Tronrud D. E., Matthews B. W. High resolution refinement of beta-galactosidase in a new crystal form reveals multiple metal-binding sites and provides a structural basis for alpha-complementation. Protein Sci. 2000 Sep;9(9):1685–1699. doi: 10.1110/ps.9.9.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Keesey J. K., Jr, Bigelis R., Fink G. R. The product of the his4 gene cluster in Saccharomyces cerevisiae. A trifunctional polypeptide. J Biol Chem. 1979 Aug 10;254(15):7427–7433. [PubMed] [Google Scholar]
  21. Labrador M., Mongelard F., Plata-Rengifo P., Baxter E. M., Corces V. G., Gerasimova T. I. Protein encoding by both DNA strands. Nature. 2001 Feb 22;409(6823):1000–1000. doi: 10.1038/35059000. [DOI] [PubMed] [Google Scholar]
  22. Lei E. P., Krebber H., Silver P. A. Messenger RNAs are recruited for nuclear export during transcription. Genes Dev. 2001 Jul 15;15(14):1771–1782. doi: 10.1101/gad.892401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Martínez-Laborda A., González-Reyes A., Morata G. Trans regulation in the Ultrabithorax gene of Drosophila: alterations in the promoter enhance transvection. EMBO J. 1992 Oct;11(10):3645–3652. doi: 10.1002/j.1460-2075.1992.tb05449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Muller M., Hagstrom K., Gyurkovics H., Pirrotta V., Schedl P. The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. Genetics. 1999 Nov;153(3):1333–1356. doi: 10.1093/genetics/153.3.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roseman R. R., Pirrotta V., Geyer P. K. The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position-effects. EMBO J. 1993 Feb;12(2):435–442. doi: 10.1002/j.1460-2075.1993.tb05675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rørth P. Gal4 in the Drosophila female germline. Mech Dev. 1998 Nov;78(1-2):113–118. doi: 10.1016/s0925-4773(98)00157-9. [DOI] [PubMed] [Google Scholar]
  28. Ullmann A., Jacob F., Monod J. Characterization by in vitro complementation of a peptide corresponding to an operator-proximal segment of the beta-galactosidase structural gene of Escherichia coli. J Mol Biol. 1967 Mar 14;24(2):339–343. doi: 10.1016/0022-2836(67)90341-5. [DOI] [PubMed] [Google Scholar]
  29. Wu C. T., Morris J. R. Transvection and other homology effects. Curr Opin Genet Dev. 1999 Apr;9(2):237–246. doi: 10.1016/S0959-437X(99)80035-5. [DOI] [PubMed] [Google Scholar]

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