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Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing

Author

Listed:
  • Shravan Kumar Mishra

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany)

  • Tim Ammon

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany)

  • Grzegorz M. Popowicz

    (NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany)

  • Marcin Krajewski

    (NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Present addresses: Institut für Biomedizinische Technik, ETH Zürich, Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland (M.K.); Enzymology Research and Development, Life Technologies, 850 Lincoln Centre Drive, Foster City, California 94404, USA (R.J.N.).)

  • Roland J. Nagel

    (Center for Molecular Biology of RNA, Cell & Developmental Biology, University of California
    Present addresses: Institut für Biomedizinische Technik, ETH Zürich, Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland (M.K.); Enzymology Research and Development, Life Technologies, 850 Lincoln Centre Drive, Foster City, California 94404, USA (R.J.N.).)

  • Manuel Ares

    (Center for Molecular Biology of RNA, Cell & Developmental Biology, University of California)

  • Tad A. Holak

    (NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany)

  • Stefan Jentsch

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany)

Abstract

Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1–HIND interaction, cannot use certain non-canonical 5′ splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier.

Suggested Citation

  • Shravan Kumar Mishra & Tim Ammon & Grzegorz M. Popowicz & Marcin Krajewski & Roland J. Nagel & Manuel Ares & Tad A. Holak & Stefan Jentsch, 2011. "Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing," Nature, Nature, vol. 474(7350), pages 173-178, June.
    • Handle: RePEc:nat:nature:v:474:y:2011:i:7350:d:10.1038_nature10143
    DOI: 10.1038/nature10143
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