3v53 | pdb_00003v53
Crystal structure of human RBM25
Structural highlights
Function[RBM25_HUMAN] RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5'-splice site (5'-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5'-ss usage through the 5'-CGGGCA-3' RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5' ss in a 5'-CGGGCA-3'-dependent manner. Binds to the exonic splicing enhancer 5'-CGGGCA-3' RNA sequence located within exon 2 of the BCL2L1 pre-mRNA.[1] Publication Abstract from PubMedHuman RBM25 (RNA-binding protein 25) is a novel splicing factor that contains a PWI domain, a newly identified RNA/DNA-binding domain, and regulates Bcl-x pre-mRNA alternative splicing. The flanking basic region has been suggested to serve as a cooperative partner of the PWI domain in the binding of nucleic acids, but the structure of this basic region is unknown. Here, we report the crystal structure of the RBM25 PWI domain and its flanking basic region. The PWI domain is revealed to comprise a conserved four-helix bundle, and the flanking basic region forms two alpha-helices and associates with helix H4 of the PWI domain. These interactions directly promote the formation of an enlarged nucleic acid-binding platform. Structure-guided mutagenesis reveals a positive charged nucleic acid-binding surface in the RBM25 PWI domain that is entirely different from that in the SRm160 PWI domain. Furthermore, we show that the promotion of the proapoptotic Bcl-x(s) isoform expression by RBM25 is facilitated by the PWI domain in vivo. Thus, our study suggests that the PWI domain plays an important role in the regulation of Bcl-x pre-mRNA alternative splicing. Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region.,Gong D, Yang F, Li F, Qian D, Wu M, Shao Z, Wu M, Wu J, Shi Y Biochem J. 2012 Nov 28. PMID:23190262[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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