Journal of Molecular Neuroscience

, Volume 15, Issue 3, pp 231–241 | Cite as

The ortholog of human ataxin-2 is essential for early embryonic patterning in C. elegans

  • Tim-Rasmus Kiehl
  • Hiroki Shibata
  • Stefan-M. Pulst


Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2) gene, is a protein of unknown function. Ataxin-2 interacts with ataxin-2-binding-protein 1 (A2BP1), a member of a novel family of putative RNA-binding proteins. Because the sequences of ataxin-2 and A2BP1 are evolutionarily conserved, we investigated functional aspects and expression pattern in the nematode Caenorhabditis elegans. Human ataxin-2 has 20.1% amino acid identity and 43.9% similarity to its C. elegans ortholog, designated ATX-2, that encodes a predicted 1026 aa protein. One of the worm orthologs of human A2BP1 is the numerator element FOX-1, with an overall 29.8% aa identity. We studied the expression pattern of atx-2 using the endogenous promotor coupled with a GFP expression vector. Atx-2 was widely expressed in the adult worm with strong expression in muscle and nervous tissue. It was also heavily expressed in the embryo. In order to elucidate the function of atx-2 and fox-1, we conducted RNA interference (RNAi) studies. The interfering dsRNA was introduced into larval L4 stage worms of the N2 strain by microinjection or soaking. DsRNA representing the full-length atx-2 gene resulted in arrested embryonic development in the offspring of all 58 microinjected worms. Nomarski imaging showed embryos in different stages of developmental arrest, indicating an essential role of atx-2 for early embryonic development. When fox-1 was targeted by RNAi, there was a marked reduction in the number of eggs per worm. The results presented here underline previous findings about the interaction of human ataxin-2 and A2BP1.

Index Entries

Ataxin-2 SCA2 C. elegans ortholog embryonic development atx-2 fox-1 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bandziulis J. B., Swanson M. S., and Dreyfuss G. (1989) RNA-binding proteins as developmental regulators. Genes Dev. 3, 431–437.PubMedGoogle Scholar
  2. Brenner S. (1974) The genetics of Caenorhabditis elegans. Genetics, 77, 71–94.PubMedGoogle Scholar
  3. Doolittle R. F., Feng, D. F., Tsang, S., Cho G., and Little, E. (1996) Determining divergence times of the major kingdoms of living organisms with a protein clock. Science 271, 470–477.PubMedCrossRefGoogle Scholar
  4. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., and Mello C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811.PubMedCrossRefGoogle Scholar
  5. Guedes S. and Priess J. R. (1997) The C. elegans MEX-1 protein is present in germline blastomeres and is a P granule component. Development 124, 731–739.PubMedGoogle Scholar
  6. Guo S. and Kemphues K. J. (1995) Par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81, 611–620.PubMedCrossRefGoogle Scholar
  7. Hermann H., Fabrizio P., Raker V. A., Foulaki K., Hornig H., Brahms H., and Luhrmann R. (1995) SnRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in protein-protein interactions. Nucleic Acids Res. 14, 2076–2088.Google Scholar
  8. Hodgkin J., Zellan J. D., and Albertson D. G. (1994) Identification of a candidate primary sex determination locus, fox-1, on the X-chromosome of Caenorhabditis elegans. Development 120, 3681–3689.PubMedGoogle Scholar
  9. Huynh D. P., Del Bigio M. R., Ho D. H., and Pulst S. M. (1999) Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer’s disease and spinocerebellar ataxia 2. Ann. Neurol. 45, 32–241.CrossRefGoogle Scholar
  10. Imbert G., Saudou F., Yvert G., Devys D., Trottier Y., Garnier J. M., Weber C., et al. (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nature Genet. 14, 285–291.PubMedCrossRefGoogle Scholar
  11. Kawasaki I., Shim Y. H., Kirchner J., Kaminker J., Wood W. B., and Strome S. (1998) PGL-1, a predicted RNA-binding component of germ granules, is essential for fertility in C. elegans. Cell 94, 635–645.PubMedCrossRefGoogle Scholar
  12. Kelly W. G., Xu S., Montgomery M. K., and Fire A. (1997) Distinct requirements for somatic and germline expression of a generally expressed Caenorhabditis elegans gene. Genetics 146, 227–238.PubMedGoogle Scholar
  13. Mello C. C., Kramer J. M., Stinchcomb D., and Ambros V. (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959–3970.PubMedGoogle Scholar
  14. Miller J. H. (1972) Experiments in Molecular Genetics. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.Google Scholar
  15. Nechiporuk T., Huynh D. P., Figueroa K., Sahba S., Nechiporuk A., and Pulst S. M. (1998) The mouse SCA2 gene: cDNA sequence, alternative splicing and protein expression. Hum. Mol. Genet. 7, 1301–1309.PubMedCrossRefGoogle Scholar
  16. Neuwald A. E. and Koonin E. V. (1998) Ataxin-2, global regulators of bacterial gene expression, and splicesomal snRNP proteins share a conserved domain. J. Mol. Med. 76, 3–5.PubMedCrossRefGoogle Scholar
  17. Nicoll M., Akerib C. C., and Meyer B. J. (1997) X-chromosome-counting mechanisms that determine nematode sex. Nature 388, 200–204.PubMedCrossRefGoogle Scholar
  18. Pulst S.-M., Nechiporuk A., Nechiporuk T., Gispert S., Chen X.-C., Lopes-Cendes I., et al. (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nature Genet. 14, 269–276.PubMedCrossRefGoogle Scholar
  19. Sanpei K., Takano H., Igarashi S., Sato T., Oyake M., Sasaki H., et al. (1996) Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nature Genet. 14, 277–284.PubMedCrossRefGoogle Scholar
  20. Shibata H., Huynh D. P., and Pulst S.-M. (2000) A novel protein with RNA binding motifs interacts with ataxin-2. Hum. Mol. Genet. 9, 1303–1313.PubMedCrossRefGoogle Scholar
  21. Skipper M., Milne C. A., and Hodgkin J. (1999) Genetic and molecular analysis of fox-1, a numerator element involved in Caenorhabditis elegans primary sex determination. Genetics 151, 617–631.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Tim-Rasmus Kiehl
    • 1
  • Hiroki Shibata
    • 1
    • 2
  • Stefan-M. Pulst
    • 1
    • 3
  1. 1.Rose Moss Laboratory for Parkinson and Neurodegenerative DiseasesBurns and Allen Research Institute, Cedars-Sinai Medical CenterLos Angeles
  2. 2.Division of Disease Genes, Institute of Genetic InformationKyushu UniversityFukuokaJapan
  3. 3.Division of Neurology, Cedars-Sinai Medical CenterUCLA School of MedicineLos Angeles

Personalised recommendations