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Cellular stress response 1 regulates RNA splicing of epidermal growth factor receptor and platelet‐derived growth factor receptor through inactivation of splicing factor 3A3
Author(s) -
Luo Jianhua,
Zuo ZeHua,
Yu Yan P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.920.4
Subject(s) - rna splicing , splicing factor , microbiology and biotechnology , rna binding protein , alternative splicing , intron , biology , rna recognition motif , fibroblast growth factor receptor 4 , exon , rna , fibroblast growth factor receptor , receptor , gene , genetics , fibroblast growth factor
Cellular stress response 1 ( CSR1 ) is a tumor suppressor gene that plays an important role in regulating cell death. In this report, we showed that the N‐terminus of CSR1 interacts with splicing factor 3A, subunit 3 ( SF3A3 ). The SF3A3 binding motif was identified in the region of amino acids 62–91 of CSR1 through cell‐free binding analyses. The interaction between CSR1 and SF3A3 led to migration of SF3A3 from nucleus to cytoplasm. The cytoplasmic redistribution of SF3A3 significantly reduced the splicing efficiency of epidermal growth factor receptor and platelet‐derived growth factor receptor. Induction of CSR1 or down‐regulation of SF3A3 also significantly reduced the splicing activity of oxytocin reporter gene both in vivo and in vitro . Mutant CSR1 that lacks the SF3A3 binding motif contained no RNA splicing regulatory activity, while the peptide corresponding to the SF3A3 binding motif in CSR1 interfered with the wild type CSR1 mediated inhibition of RNA splicing. Interaction of CSR1 and SF3A3 is essential for CSR1 mediated cell death. To our knowledge, this is the first report demonstrating that RNA splicing is negatively regulated by redistribution of a splicing factor. Support or Funding Information National Cancer Institute (RO1 CA098249)