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. 1999 Sep;153(1):117–134. doi: 10.1093/genetics/153.1.117

Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans.

A G Davies 1, C A Spike 1, J E Shaw 1, R K Herman 1
PMCID: PMC1460726  PMID: 10471705

Abstract

Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym-1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The phenotypes of sym single mutants are essentially wild type. mec-8; sym-1 embryos arrest during embryonic elongation and exhibit defects in the attachment of body muscle to extracellular cuticle. sym-1 can encode a protein containing a signal sequence and 15 contiguous leucine-rich repeats. A fusion of sym-1 and the gene for green fluorescent protein rescued the synthetic lethality of mec-8; sym-1 mutants; the fusion protein was secreted from the apical hypodermal surface of the embryo. We propose that SYM-1 helps to attach body muscle to the extracellular cuticle and that another gene that is dependent upon mec-8 for pre-mRNA processing overlaps functionally with sym-1. RNA-mediated interference experiments indicated that a close relative of sym-1 functionally overlaps both sym-1 and mec-8 in affecting muscle attachment. sym-2, sym-3, and sym-4 appear to provide additional functions that are essential in the absence of mec-8(+).

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Selected References

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

  1. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bender A., Pringle J. R. Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Mar;11(3):1295–1305. doi: 10.1128/mcb.11.3.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birney E., Kumar S., Krainer A. R. Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res. 1993 Dec 25;21(25):5803–5816. doi: 10.1093/nar/21.25.5803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brookfield J. F. Genetic redundancy. Adv Genet. 1997;36:137–155. doi: 10.1016/s0065-2660(08)60308-9. [DOI] [PubMed] [Google Scholar]
  6. C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
  7. Chalfie M., Au M. Genetic control of differentiation of the Caenorhabditis elegans touch receptor neurons. Science. 1989 Feb 24;243(4894 Pt 1):1027–1033. doi: 10.1126/science.2646709. [DOI] [PubMed] [Google Scholar]
  8. Chalfie M., Sulston J. Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol. 1981 Mar;82(2):358–370. doi: 10.1016/0012-1606(81)90459-0. [DOI] [PubMed] [Google Scholar]
  9. Chalfie M., Tu Y., Euskirchen G., Ward W. W., Prasher D. C. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. doi: 10.1126/science.8303295. [DOI] [PubMed] [Google Scholar]
  10. Clark S. G., Lu X., Horvitz H. R. The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. Genetics. 1994 Aug;137(4):987–997. doi: 10.1093/genetics/137.4.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cooke J., Nowak M. A., Boerlijst M., Maynard-Smith J. Evolutionary origins and maintenance of redundant gene expression during metazoan development. Trends Genet. 1997 Sep;13(9):360–364. doi: 10.1016/s0168-9525(97)01233-x. [DOI] [PubMed] [Google Scholar]
  12. Coulson A., Huynh C., Kozono Y., Shownkeen R. The physical map of the Caenorhabditis elegans genome. Methods Cell Biol. 1995;48:533–550. doi: 10.1016/s0091-679x(08)61402-8. [DOI] [PubMed] [Google Scholar]
  13. Culotti J. G., Von Ehrenstein G., Culotti M. R., Russell R. L. A second class of acetylcholinesterase-deficient mutants of the nematode Caenorhabditis elegans. Genetics. 1981 Feb;97(2):281–305. doi: 10.1093/genetics/97.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eeckman F. H., Durbin R. ACeDB and macace. Methods Cell Biol. 1995;48:583–605. [PubMed] [Google Scholar]
  15. Efimov V. P., Morris N. R. A screen for dynein synthetic lethals in Aspergillus nidulans identifies spindle assembly checkpoint genes and other genes involved in mitosis. Genetics. 1998 May;149(1):101–116. doi: 10.1093/genetics/149.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ferguson E. L., Horvitz H. R. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985 May;110(1):17–72. doi: 10.1093/genetics/110.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ferguson E. L., Horvitz H. R. The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways. Genetics. 1989 Sep;123(1):109–121. doi: 10.1093/genetics/123.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
  19. Francis R., Waterston R. H. Muscle cell attachment in Caenorhabditis elegans. J Cell Biol. 1991 Aug;114(3):465–479. doi: 10.1083/jcb.114.3.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Guo S., Kemphues K. J. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell. 1995 May 19;81(4):611–620. doi: 10.1016/0092-8674(95)90082-9. [DOI] [PubMed] [Google Scholar]
  21. Harfe B. D., Fire A. Muscle and nerve-specific regulation of a novel NK-2 class homeodomain factor in Caenorhabditis elegans. Development. 1998 Feb;125(3):421–429. doi: 10.1242/dev.125.3.421. [DOI] [PubMed] [Google Scholar]
  22. Hedgecock E. M., Culotti J. G., Thomson J. N., Perkins L. A. Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Dev Biol. 1985 Sep;111(1):158–170. doi: 10.1016/0012-1606(85)90443-9. [DOI] [PubMed] [Google Scholar]
  23. Herman R. K., Albertson D. G., Brenner S. Chromosome rearrangements in Caenorhabditis elegans. Genetics. 1976 May;83(1):91–105. doi: 10.1093/genetics/83.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hilkens J., Ligtenberg M. J., Vos H. L., Litvinov S. V. Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci. 1992 Sep;17(9):359–363. doi: 10.1016/0968-0004(92)90315-z. [DOI] [PubMed] [Google Scholar]
  25. Hodgkin J., Herman R. K. Changing styles in C. elegans genetics. Trends Genet. 1998 Sep;14(9):352–357. doi: 10.1016/s0168-9525(98)01543-1. [DOI] [PubMed] [Google Scholar]
  26. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  27. Hresko M. C., Williams B. D., Waterston R. H. Assembly of body wall muscle and muscle cell attachment structures in Caenorhabditis elegans. J Cell Biol. 1994 Feb;124(4):491–506. doi: 10.1083/jcb.124.4.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Huang L. S., Tzou P., Sternberg P. W. The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. Mol Biol Cell. 1994 Apr;5(4):395–411. doi: 10.1091/mbc.5.4.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Johnson C. D., Rand J. B., Herman R. K., Stern B. D., Russell R. L. The acetylcholinesterase genes of C. elegans: identification of a third gene (ace-3) and mosaic mapping of a synthetic lethal phenotype. Neuron. 1988 Apr;1(2):165–173. doi: 10.1016/0896-6273(88)90201-2. [DOI] [PubMed] [Google Scholar]
  30. Kajava A. V. Structural diversity of leucine-rich repeat proteins. J Mol Biol. 1998 Apr 3;277(3):519–527. doi: 10.1006/jmbi.1998.1643. [DOI] [PubMed] [Google Scholar]
  31. Kobe B., Deisenhofer J. The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci. 1994 Oct;19(10):415–421. doi: 10.1016/0968-0004(94)90090-6. [DOI] [PubMed] [Google Scholar]
  32. Lambie E. J., Kimble J. Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development. 1991 May;112(1):231–240. doi: 10.1242/dev.112.1.231. [DOI] [PubMed] [Google Scholar]
  33. Lu X., Horvitz H. R. lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48. Cell. 1998 Dec 23;95(7):981–991. doi: 10.1016/s0092-8674(00)81722-5. [DOI] [PubMed] [Google Scholar]
  34. Lundquist E. A., Herman R. K., Rogalski T. M., Mullen G. P., Moerman D. G., Shaw J. E. The mec-8 gene of C. elegans encodes a protein with two RNA recognition motifs and regulates alternative splicing of unc-52 transcripts. Development. 1996 May;122(5):1601–1610. doi: 10.1242/dev.122.5.1601. [DOI] [PubMed] [Google Scholar]
  35. Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Meneely P. M., Herman R. K. Lethals, steriles and deficiencies in a region of the X chromosome of Caenorhabditis elegans. Genetics. 1979 May;92(1):99–115. doi: 10.1093/genetics/92.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Miller D. M., 3rd, Ortiz I., Berliner G. C., Epstein H. F. Differential localization of two myosins within nematode thick filaments. Cell. 1983 Sep;34(2):477–490. doi: 10.1016/0092-8674(83)90381-1. [DOI] [PubMed] [Google Scholar]
  38. Moerman D. G., Hutter H., Mullen G. P., Schnabel R. Cell autonomous expression of perlecan and plasticity of cell shape in embryonic muscle of Caenorhabditis elegans. Dev Biol. 1996 Jan 10;173(1):228–242. doi: 10.1006/dbio.1996.0019. [DOI] [PubMed] [Google Scholar]
  39. Park E. C., Horvitz H. R. Mutations with dominant effects on the behavior and morphology of the nematode Caenorhabditis elegans. Genetics. 1986 Aug;113(4):821–852. doi: 10.1093/genetics/113.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Perkins L. A., Hedgecock E. M., Thomson J. N., Culotti J. G. Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol. 1986 Oct;117(2):456–487. doi: 10.1016/0012-1606(86)90314-3. [DOI] [PubMed] [Google Scholar]
  41. Rogalski T. M., Gilchrist E. J., Mullen G. P., Moerman D. G. Mutations in the unc-52 gene responsible for body wall muscle defects in adult Caenorhabditis elegans are located in alternatively spliced exons. Genetics. 1995 Jan;139(1):159–169. doi: 10.1093/genetics/139.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Stiles J. I. Use of integrative transformation of yeast in the cloning of mutant genes and large segments of contiguous chromosomal sequences. Methods Enzymol. 1983;101:290–300. doi: 10.1016/0076-6879(83)01022-8. [DOI] [PubMed] [Google Scholar]
  44. Thomas J. H. Thinking about genetic redundancy. Trends Genet. 1993 Nov;9(11):395–399. doi: 10.1016/0168-9525(93)90140-d. [DOI] [PubMed] [Google Scholar]
  45. Zhang B., Gallegos M., Puoti A., Durkin E., Fields S., Kimble J., Wickens M. P. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature. 1997 Dec 4;390(6659):477–484. doi: 10.1038/37297. [DOI] [PubMed] [Google Scholar]

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