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The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins

Nature Genetics volume 12, pages 260–265 (1996)Cite this article

Abstract

The mouse quaking gene, essential for nervous system myelination and survival of the early embryo has been positionally cloned. Its sequence implies that the locus encodes a multifunctional gene used in a specific set of developing tissues to unite signal transduction with some aspect of RNA metabolism. The quakingviable (qkv) mutation has one class of messages truncated by a deletion. An independent ENU-induced mutation has a nonconservative amino acid change in one of two newly identified domains that are conserved from the C. elegans gld-1 tumour suppressor gene to the human Src-associated protein Sam68. The size and conservation of the quaking gene family implies that the pathway defined by this mutation may have broad relevance for rapid conveyance of extracellular information directly to primary gene transcripts.

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References

  1. Bennett, D. Developmental analysis of a mutation with pleiottopic effects in the mouse. J. Morph. 96, 199–234 (1956).

    Article  Google Scholar 

  2. Sidman, R.L., Dickie, M.M. & Appel, S.H. Mutant mice (quaking and jimpy) with deficient myelination in the central nervous system. Science. 144, 309–311 (1964).

    Article  CAS  Google Scholar 

  3. Friedrich, Jr V.L. The myelin deficit in quaking mice. Brain Res. 82, 168–172 (1974).

    Article  Google Scholar 

  4. Bennett, W.J., Gall, A.M., Southard, J.L. & Sidman, R.L. Abnormal spermtogenesis in quaking, a myelin-deficient mutant mouse. Biol. Reprod. 5, 30–58 (1971).

    Article  CAS  Google Scholar 

  5. Ebersole, T., Rho, O. & Artzt, K. The proximal end of mouse chromosome 17: New molecular markers identify a deletion associated with quakingviable. Genetics. 131, 183–190 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bode, V.C. Ethylnitrosourea mutagenesis and the isolation of mutant alleles for specific genes located in the T region of mouse chromosome 17. Genetics 108, 457–470 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Justice, M.J. & Bode, V.C. Induction of new mutations in a mouse t-haplotype using ethylnttrosourea mutagenesis. Genet. Res. Camb. 47, 187–192 (1986).

    Article  CAS  Google Scholar 

  8. Shedlovsky, A., King, T.R. & Dove, W.F. Saturation germ line mutagenesis of the murine t region including a lethal allele at the quaking locus. Proc. Natl. Acad. Sci. USA. 85, 180–184 (1988).

    Article  CAS  Google Scholar 

  9. Justice, M.J. & Bode, V.C., ENU-induced alleles of the murine quaking locus are recessive embryonic lethal mutations. Genet. Res. Camb. 51, 95–102 (1988).

    Article  CAS  Google Scholar 

  10. Gibson, T.J., Thompson, J.D. & Heringa, J. The KH domain occurs in a diverse set of RNA-binding proteins that include the antiterminator NusA and is probably involved in binding to nucleic acid. FEBS. 324, 361–366 (1993).

    Article  CAS  Google Scholar 

  11. Siomi, H., Matunis, M.J., Michael, W.M. & Dreyfuss, G. The pre-mRNA binding K protein contains a novel evolutionary conserved motif. Nucl. Adds Res. 21, 1193–1198 (1993).

    Article  CAS  Google Scholar 

  12. Burd, C.G. & Dreyfuss, G. Conserved structures and diversity of functions of RNA-blndingproteins. science 266, 615–621 (1994).

    Article  Google Scholar 

  13. Wong, G. et al. Molecular cloning and nucleic acid binding properties of the GAP-associated Tyrosine Phosphoprotein p62. Cell 69, 551–558 (1992).

    Article  CAS  Google Scholar 

  14. Fumagalli, S., Totty, N.F., Hsuan, J.J. & Courtneidge, S.A. A target for Src in mitosis. Nature 368, 871–874 (1994).

    Article  CAS  Google Scholar 

  15. Taylor, S.J. & ShaJloway, D., RNA-bindlng protein associated with Src through its SH2 and SH3 domains in mitosis. Nature. 368, 867–871 (1994).

    Article  CAS  Google Scholar 

  16. Ogawa, W., Hosomi, Y., Shii, K. & Roth, R.A. Evidence for two distinct 60-kilodalton substrates of the SRC tyrosine kinase. J. Biol. Chem. 289, 29602–29608 (1994).

    Google Scholar 

  17. Jones, A.R. & Schedl, T. Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68. Genes Devel. 9, 1491–1504 (1995).

    Article  CAS  Google Scholar 

  18. Kiledjian, M. & Dreyfuss, G. Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. EMBO J. 11, 2655–2664 (1992).

    Article  CAS  Google Scholar 

  19. Yu, H. et al. Structural basis for the binding of proline-rich peptides to SH3 domains. Cell 76, 933–945 (1994).

    Article  CAS  Google Scholar 

  20. Feng, S., Chen, J.K., Yu, H., Simon, J.A. & Schreiber, S.L. Two binding orientations for peptides to the Src SH3 domain: Development of a general model for SH3-llgand interactions. Science 266, 1241–1247 (1994).

    Article  CAS  Google Scholar 

  21. Weng, Z. et al. Identification of Src, Fyn, and Lyn SHS-binding proteins: Implications for a function of SH3 domains. Mol. Cell. Biol. 14, 4509–4521 (1994).

    Article  CAS  Google Scholar 

  22. Hobert, 0., JaJal, B., Schlessinger, J. & Ulrich, A. Novel signaling pathway suggested by SH3 domain-mediated p95vav/heterogeneous ribonucleoprotein K interaction. J. Biol. Chem. 269, 20225–20228 (1994).

    CAS  PubMed  Google Scholar 

  23. Ashley, C.T. et al. Human and murine FMR-1: Alternative splicing and translational initiation downstream of the CGG-repeat. Nature Genet. 4, 244–251 (1994).

    Article  Google Scholar 

  24. Siomi, H., Choi, M., Siomi, M.C., Nussbaum, R.L. & Dreyfuss, G. Essential role for KH domains in RNA binding: Impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome. Cell 77, 33–39 (1994).

    Article  CAS  Google Scholar 

  25. Timsit, S., Martinez, S., Allinquant, B., Peyron, F., Puelles, L. & Zalc, B. Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. J. Neurosci. 15, 1012–1024 (1995).

    Article  CAS  Google Scholar 

  26. Darnell, Jr J.E., Kerr, M. & Stark, G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 264, 1415–1421 (1994).

    Article  CAS  Google Scholar 

  27. Umemori, H., Sato, S., Yagi, T., Aizawa, S & Yamamoto, T. Initial events of myelination involve Fyn tyrosine kinase signalling. Nature 367, 572–576 (1994).

    Article  CAS  Google Scholar 

  28. Richard, S. et al. Association of p62, a multifunctional SH2-binding and SH3-binding protein, with src family tyrosine kinases, Grb2, and phospholipase Cλ-1. Mol. Cell. Biol. 15, 186–197 (1995).

    Article  CAS  Google Scholar 

  29. Hill, M.A., Schedlich, L. & Gunning, P. Serum-induced signal transduction determines the peripheral location of β-actin mRNA within the cell. J.Cell.Biol. 126, 1221–1230 (1994).

    Article  CAS  Google Scholar 

  30. Steward, O. Dendrites as compartments for macromolecular synthesis. Proc. Natl. Acad. Sci. USA 91, 10766–10768 (1994).

    Article  CAS  Google Scholar 

  31. Mayeda, A., Munroe, S.H., Cáceres, J.F. & Krainer, A.R. Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins. EMBO J. 13, 5483–5495 (1994).

    Article  CAS  Google Scholar 

  32. Fujita, N. et al. Developmentally regulated alternative splicing of brain myelin-associated glycoprotein mRNA is lacking in the quaking mouse. FEBS. 232, 323–327 (1988).

    Article  CAS  Google Scholar 

  33. Fujita, N. et al. The large isoform of myelin-associated glycoprotein is scarcely expressed in the quaking mouse brain. J. Neurochem. 55, 1056–1059 (1990).

    Article  CAS  Google Scholar 

  34. Campagnoni, A.T. et al. Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. J. Biol. Chem. 268, 4930–4938 (1993).

    CAS  PubMed  Google Scholar 

  35. Ikenaka, K., Kagawa, T. & Mikoshiba, K. Selective expression of DM-20, an alternatively spliced myelin proteolipid gene product, in developing nervous sytem of the mouse. J. Neurochem. 58, 2248–2253 (1992).

    Article  CAS  Google Scholar 

  36. DeWille, J.W. & Farmer, S.J. Quaking phenotype influences brain lipid-related mRNA levels. Neurosci. Lett. 141, 195–198 (1992).

    Article  CAS  Google Scholar 

  37. Crenshaw III, E.B., Russo, A.F., Swanson, L.W. & Rosenfeld, M.G. Neuron-specific alternative RNA processing in transgenic mice expressing a methallothionein-calcitonin fusion gene. Cell 49, 389–398 (1987).

    Article  CAS  Google Scholar 

  38. Rossi, J.M. et al. Genomic analysis using a yeast artificial chromosome library with mouse DNA inserts. Proc. Natl. Acad. Sci. USA 89, 2456–2460 (1992).

    Article  CAS  Google Scholar 

  39. Riley, J. et al. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucl. Acids Res. 18, 2887–2890 (1990).

    Article  CAS  Google Scholar 

  40. Enrich, E., Craig, A., Poustka, A., Frischauf, A.-M. & Lehrach, H. A family of cosmid vectors with the multi-copy R6K replication origin. Gene 57, 229–237 (1987).

    Article  Google Scholar 

  41. Wilkinson, D.G. Whole mount in situ hybridization of vertebrate embryos. In situ Hybridization, A Practical Approach (ed Wilkinson, D.G.) 75–83 (IRL Press, New York, 1992).

    Google Scholar 

  42. Yan, Y., Lagenaur, C. & Narayanan, V. Molecular cloning of M6: Identification of a PLP/DM20 gene family. Neuron. 11, 423–431 (1993).

    Article  CAS  Google Scholar 

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Author information

Author notes

  1. Thomas A. Ebersole

    Present address: Department of Genetics, Cambridge University, Cambridge, CB2 3EH, UK

  2. Qi Chen

    Present address: Genentech, 460 Point San Bruno Blvd., South San Francisco, California, 94080, USA

  3. Monica J. Justice

    Present address: Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831, USA

Authors and Affiliations

  1. Department of Zoology, The University of Texas at Austin, Austin, Texas, 78712-1064, USA

    Thomas A. Ebersole, Qi Chen & Karen Artzt

  2. Division of Biology, Kansas State University, Manhattan, Kansas, 66506, USA

    Monica J. Justice

Authors
  1. Thomas A. Ebersole
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  2. Qi Chen
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  3. Monica J. Justice
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  4. Karen Artzt
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Ebersole, T., Chen, Q., Justice, M. et al. The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins. Nat Genet 12, 260–265 (1996). https://doi.org/10.1038/ng0396-260

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