Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region

Human RBM25 (RNA-binding motif 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 co-operative partner of the PWI domain in the bin...

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Main Authors:	Gong, Deshun, Yang, Fan, Li, Fudong, Qian, Dandan, Wu, Minhao, Shao, Zhenhua, Wu, Mian, Wu, Jihui, Shi, Yunyu
Format:	Online
Language:	English
Published:	Portland Press Ltd. 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553564/

id	pubmed-3553564
recordtype	oai_dc
spelling	pubmed-35535642013-01-28 Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region Gong, Deshun Yang, Fan Li, Fudong Qian, Dandan Wu, Minhao Shao, Zhenhua Wu, Mian Wu, Jihui Shi, Yunyu Research Article Human RBM25 (RNA-binding motif 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 co-operative partner of the PWI domain in the binding of nucleic acids, but the structure of this basic region is unknown. In the present paper, 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 α-helices and associates with helix H4 of the PWI domain. These interactions promote directly the formation of an enlarged nucleic-acid-binding platform. Structure-guided mutagenesis reveals a positively 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 pro-apoptotic Bcl-xS isoform expression by RBM25 is facilitated by the PWI domain in vivo. Thus the present study suggests that the PWI domain plays an important role in the regulation of Bcl-x pre-mRNA alternative splicing. Portland Press Ltd. 2013-01-24 2013-02-15 /pmc/articles/PMC3553564/ /pubmed/23190262 http://dx.doi.org/10.1042/BJ20121382 Text en © 2013 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gong, Deshun Yang, Fan Li, Fudong Qian, Dandan Wu, Minhao Shao, Zhenhua Wu, Mian Wu, Jihui Shi, Yunyu
spellingShingle	Gong, Deshun Yang, Fan Li, Fudong Qian, Dandan Wu, Minhao Shao, Zhenhua Wu, Mian Wu, Jihui Shi, Yunyu Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
author_facet	Gong, Deshun Yang, Fan Li, Fudong Qian, Dandan Wu, Minhao Shao, Zhenhua Wu, Mian Wu, Jihui Shi, Yunyu
author_sort	Gong, Deshun
title	Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
title_short	Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
title_full	Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
title_fullStr	Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
title_full_unstemmed	Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region
title_sort	crystal structure and functional characterization of the human rbm25 pwi domain and its flanking basic region
description	Human RBM25 (RNA-binding motif 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 co-operative partner of the PWI domain in the binding of nucleic acids, but the structure of this basic region is unknown. In the present paper, 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 α-helices and associates with helix H4 of the PWI domain. These interactions promote directly the formation of an enlarged nucleic-acid-binding platform. Structure-guided mutagenesis reveals a positively 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 pro-apoptotic Bcl-xS isoform expression by RBM25 is facilitated by the PWI domain in vivo. Thus the present study suggests that the PWI domain plays an important role in the regulation of Bcl-x pre-mRNA alternative splicing.
publisher	Portland Press Ltd.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553564/
_version_	1611949216421117952

Crystal structure and functional characterization of the human RBM25 PWI domain and its flanking basic region

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