SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome

Venables, Julian P.; Dalgliesh, Caroline; Paronetto, Maria Paolo; Skitt, Lindi; Thornton, Jared K.; Saunders, Philippa T.; Sette, Claudio; Jones, Keith T.; Elliott, David J.

Title: SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome
Creator: Venables, Julian P.; Dalgliesh, Caroline; Paronetto, Maria Paolo; Skitt, Lindi; Thornton, Jared K.; Saunders, Philippa T.; Sette, Claudio; Jones, Keith T.; Elliott, David J.
Relation: Human Molecular Genetics Vol. 13, Issue 14, p. 1525-1534
Publisher Link: http://dx.doi.org/10.1093/hmg/ddh165
Publisher: Oxford University Press
Resource Type: journal article
Date: 2004
Description: 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.
Subject: proteasome; mouse; gene; meiosis; T-STAR; cells; RNA; proteins
Identifier: uon:6573
Identifier: http://hdl.handle.net/1959.13/804280
Identifier: ISSN:0964-6906
Language: eng
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