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REVIEW
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 21-25

Split End Family RNA Binding Proteins: Novel Tumor Suppressors Coupling Transcriptional Regulation with RNA Processing


1 Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, The University of Alabama at Birmingham, Birmingham, AL, USA
2 Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China

Correspondence Address:
Dr. Xinyang Zhao
1825 University Boulevard, SHEL 703, Birmingham, AL 35294
USA
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Source of Support: None, Conflict of Interest: None


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Split End (SPEN) family proteins have three members: SPEN, RBM15, and RBM15B. SPEN family proteins contain three conserved RNA recognition motifs on the N-terminal region and an SPOC domain on the C-terminal region. RBM15 is fused to MKL1 in chromosome translocation t (1;22), which causes childhood acute megakaryoblastic leukemia (AMKL). Haploinsufficiency of RBM15 in AMKL indicates that RBM15 is a tumor suppressor. Both SPEN and RBM15 are mutated in a variety of cancer types, implying that they are tumor suppressors. SPEN and RBM15are required for the development of multiple organs including hematopoiesis partly via regulating the NOTCH signaling pathway, as well as the WNT signaling pathway in species ranging from Drosophila to mammals. Besides transcriptional regulation, RBM15 regulates RNA export and RNA splicing. In this review, we summarized data in the literature on how the members in SPEN family regulate gene expression at transcription and RNA processing steps. The crosstalk between epigenetic regulation and RNA metabolism is increasingly appreciated in understanding tumorigenesis. Studying the SPEN family of RNA binding proteins will create new perspectives for cancer therapy.


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