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A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells

Nature Genetics volume 22, pages 171–174 (1999)Cite this article

Abstract

Chromatin packaging in mammalian spermatozoa requires an ordered replacement of the somatic histones by two classes of spermatid-specific basic proteins, the transition proteins and the protamines1. Temporal expression of transition proteins and protamines during spermatid differentiation is under translational control, and premature translation of protamine 1 leads to precocious nuclear condensation and sterility2. We have previously suggested that the double-stranded (ds) RNA binding protein Prbp (encoded by the gene Tarbp2) functions as a translational regulator during mouse spermatogenesis3. Here we show that Prbp is required for proper translational activation of the mRNAs encoding the protamines. We generated mice that carry a targeted disruption of Tarbp2 and determined that they were sterile and severely oligospermic. Using immunohistological analysis, we determined that the endogenous Prm2 mRNA and a reporter mRNA carrying protamine 1 translational-control elements were translated in a mosaic pattern. We showed that failure to synthesize the protamines resulted in delayed replacement of the transition proteins and subsequent failure of spermiation. The timing of Prbp expression suggests that it may function as a chaperone in the assembly of specific translationally regulated ribonucleoprotein particles.

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Figure 1: Epididymal and testicular histology in Tarbp2-/- mice.
Figure 2: Mosaic patterns of translation in Tarbp2–/– testis.
Figure 3: In situ hybridization and immunohistochemistry of GH1, Tnp2 and Prm2.
Figure 4: Mosaic co-localization of GH1 and Prm2.
Figure 5: Analysis of total testis basic proteins.

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References

  1. Meistrich, M.L. in Molecular Biology of the Male Reproductive System (ed. Kretser, D.M.) 67–97 (Academic Press, San Diego, 1993).

    Google Scholar 

  2. Lee, K., Haugen, H.S., Clegg, C.H. & Braun, R.E. Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proc. Natl Acad. Sci. USA 92, 12451–12455 (1995).

    Article  CAS  Google Scholar 

  3. Lee, K., Fajardo, M.A. & Braun, R.E. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor. Mol. Cell. Biol. 16, 3023–3034 (1996).

    Article  CAS  Google Scholar 

  4. St Johnston, D., Brown, N.H., Gall, J.G. & Jantsch, M. A conserved double-stranded RNA-binding domain. Proc. Natl Acad. Sci. USA 89, 10979–10983 (1992).

    Article  CAS  Google Scholar 

  5. Braun, R.E. Temporal translational regulation of the protamine 1 gene during mouse spermatogenesis. Enzyme 44, 120–128 (1990).

    Article  CAS  Google Scholar 

  6. Gatignol, A., Buckler, W.A., Berkhout, B. & Jeang, K.T. Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science 251, 1597– 1600 (1991).

    Article  CAS  Google Scholar 

  7. Park, H. et al. TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR. Proc. Natl Acad. Sci. USA 91, 4713–4717 (1994).

    Article  CAS  Google Scholar 

  8. Gatignol, A., Buckler, C. & Jeang, K.T. Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen. Mol. Cell. Biol. 13, 2193– 2202 (1993).

    Article  CAS  Google Scholar 

  9. Fajardo, M.A., Haugen, H.S., Clegg, C.H. & Braun, R.E. Separate elements in the 3´ untranslated region of the mouse protamine 1 mRNA regulate translational repression and activation during murine spermatogenesis. Dev. Biol. 191, 42–52 (1997).

    Article  CAS  Google Scholar 

  10. Fajardo, M.A., Butner, K.A., Lee, K. & Braun, R.E. Germ cell-specific proteins interact with the 3´ untranslated regions of Prm1 and Prm2 mRNA. Dev. Biol. 166, 643– 653 (1994).

    Article  CAS  Google Scholar 

  11. Stanker, L.H., Wyrobek, A., McKeown, C. & Balhorn, R. Identification of the binding site of two monoclonal antibodies to human protamine. Mol. Immunol. 30, 1633–1638 (1993).

    Article  CAS  Google Scholar 

  12. Alfonso, P.J. & Kistler, W.S. Immunohistochemical localization of spermatid nuclear transition protein 2 in the testes of rats and mice. Biol. Reprod. 48, 522– 529 (1993).

    Article  CAS  Google Scholar 

  13. Schumacher, J.M., Lee, K., Edelhoff, S. & Braun, R.E. Distribution of Tenr, an RNA binding protein, in a lattice-like network within the spermatid nucleus in the mouse. Biol. Reprod. 52, 1274–1283 (1995).

    Article  CAS  Google Scholar 

  14. Leblond, C.P. & Clermont, Y. Spermiogensis of rat, mouse, hamster and guinea pig as revealed by the "periodic acid-fuschin sulfurous acid" technique. Am. J. Anat. 90, 167–216 (1952).

    Article  CAS  Google Scholar 

  15. Oakberg, E.F. A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am. J. Anat. 99, 391–413 ( 1956).

    Article  CAS  Google Scholar 

  16. Russell, L.D., Ettlin, R.A., SinhaHikim, A.P. & Clegg, E.D. Histological and Histopathological Evaluation of the Testis (Cache River Press, Clearwater, Florida, 1990).

    Google Scholar 

  17. Braun, R.E., Peschon, J.J., Behringer, R.R., Brinster, R.L. & Palmiter, R.D. Protamine 3´-untranslated sequences regulate temporal translational control and subcellular localization of growth hormone in spermatids of transgenic mice. Genes Dev. 3, 793–802 ( 1989).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants to REB from the NIH/NICHD (HD27215) and (U54 HD12629), the latter through a cooperative agreement as part of the Specialized Cooperative Centers Program in Reproduction Research. A.H.F.M.P. was supported by a TALENT fellowship from the Netherlands Organization for Scientific Research and from the Mellon Foundation.

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  1. Department of Genetics, Box 357360, 1959 NE Pacific

    Jun Zhong, Antoine H.F.M. Peters, Keesook Lee & Robert E. Braun

  2. University of Washington, Seattle, 98195, Washington, USA

    Jun Zhong, Antoine H.F.M. Peters, Keesook Lee & Robert E. Braun

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  1. Jun Zhong
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Correspondence to Robert E. Braun.

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Zhong, J., Peters, A., Lee, K. et al. A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells. Nat Genet 22, 171–174 (1999). https://doi.org/10.1038/9684

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