2004, English, Article, Journal or magazine article edition: SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome Venables, Julian P.; Dalgliesh, Caroline; Paronetto, Maria Paolo; ...

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Physical Description
  • journal article
Published
  • Oxford University Press, 2004
Language
  • English

Edition details

Title
  • SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome
Author
  • Venables, Julian P.
  • Dalgliesh, Caroline
  • Paronetto, Maria Paolo
  • Skitt, Lindi
  • Thornton, Jared K.
  • Saunders, Philippa T.
  • Sette, Claudio
  • Jones, Keith T.
  • Elliott, David J.
Published
  • Oxford University Press, 2004
Physical Description
  • journal article
Subjects
Summary
  • T-STAR is one of three members of the SAM68 family of RNA-binding proteins that have been shown to be involved in various gene expression pathways including the control of pre-mRNA splicing. We employed a two-hybrid screen to identify proteins that interact with human T-STAR. The predominant interacting proteins were the E3 ubiquitin ligases SIAH1 and SIAH2. We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation. Rodent T-STAR orthologues (also known as etoile or SLM2) were not targeted for degradation by SIAH1. However a double amino acid substitution of mouse T-STAR that mimics the human SIAH1-binding site brought mouse T-STAR under in vivo control of SIAH1. Using a minigene transfection assay for alternative splicing activity we showed that human T-STAR, like its rodent orthologues can influence splice site choice and that human, but not mouse, T-STAR-dependent alternative splicing is modulated by SIAH1. Western blots of protein from purified germ cells indicated that SIAH1 protein expression peaks in meiosis. In mouse, T-STAR is co-expressed with SIAH1 during meiosis but, in humans, T-STAR is only strongly expressed after meiosis. Comparative sequence analysis showed SIAH-mediated proteasomal degradation of T-STAR has evolved in the primate lineage. Collectively these data suggest that SIAH-mediated down regulation of alternative splicing may be an important developmental difference between otherwise highly conserved T-STAR proteins.
Language
  • English
Related Resource
Identifier
  • oai:novaprd.newcastle.edu.au:uon:6573
  • ISSN:0964-6906

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