Open AccessTLS-ERG Leukemia Fusion Protein Inhibits RNA Splicing Mediated by Serine-Arginine Proteins
Author(s) -
Liu Yang,
Lisa J. Embree,
Dennis D. Hickstein
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.10.3345-3354.2000
Subject(s) - sr protein , biology , fusion protein , rna splicing , microbiology and biotechnology , alternative splicing , rna binding protein , fusion gene , messenger rna , rna , gene , genetics , recombinant dna
The translocation liposarcoma (TLS ) gene is fused to the ETS-related gene (ERG ) in human myeloid leukemia, resulting in the generation of a TLS-ERG protein. We demonstrate that both TLS and the TLS-ERG leukemia fusion protein bind to RNA polymerase II through the TLS N-terminal domain, which is retained in the fusion protein; however, TLS recruits members of the serine-arginine (SR) family of splicing factors through its C-terminal domain, whereas the TLS-ERG fusion protein lacks the ability to recruit SR proteins due to replacement of the C-terminal domain by the fusion partner ERG. In transient-transfection assays, the TLS-ERG fusion protein inhibits E1A pre-mRNA splicing mediated by these TLS-associated SR proteins (TASR), and stable expression of the TLS-ERG fusion protein in K562 cells alters the splicing profile of CD44 mRNA. These results suggest that TLS fusion proteins may lead to cellular abnormalities by interfering with the splicing of important cellular regulators.