Regulation of alternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein H
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概要
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Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor. The binding of ligands to membrane-bound RAGE (mRAGE) evokes cellular responses involved in various pathological processes. Previously, we identified a novel soluble form, endogenous secretory RAGE (esRAGE) generated by alternative 5′ splice site selection in intron 9 that leads to extension of exon 9 (exon 9B). Because esRAGE works as an antagonistic decoy receptor, the elucidation of regulatory mechanism of the alternative splicing is important to understand RAGE-related pathological processes. Here, we identified G-rich cis-elements within exon 9B for regulation of the alternative splicing using a RAGE minigene. Mutagenesis of the G-rich cis-elements caused a drastic increase in the esRAGE/mRAGE ratio in the minigene-transfected cells and in loss of binding of the RNA motif to heterogenous nuclear ribonucleoprotein (hnRNP) H. On the other hand, the artificial introduction of a G-stretch in exon 9B caused a drastic decrease in the esRAGE/mRAGE ratio accompanied by the binding of hnRNP H to the RNA motif. Thus, the G-stretches within exon 9B regulate RAGE alternative splicing via interaction with hnRNP H. The findings should provide a molecular basis for the development of medicines for RAGE-related disorders that could modulate esRAGE/mRAGE ratio. © The Authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
- Oxford University Press / Japanese Biochemical Society = 日本生化学会の論文
- 2010-05-01
著者
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Yamamoto Yasuhiko
Department of Chemistry, University of Tsukuba
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YAMAMOTO Hiroshi
Department of Macromolecular Science, Graduate School of Science, Osaka University
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Yamamoto Yasuhiko
Department Of Biochemistry And Molecular Vascular Biology Kanazawa University Graduate School Of Med
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WATANABE Takuo
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Me
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OHE Kazuyo
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Me
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YONEKURA Hideto
Department of Biochemistry, Kanazawa Medical University, School of Medicine
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HARADA Shin-ichi
Center for Biomedical Research and Education, School of Medicine, Kanazawa University
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Ohe Kazuyo
Department Of Biochemistry And Molecular Vascular Biology Kanazawa University Graduate School Of Med
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Yonekura Hideto
Department Of Biochemistry Kanazawa Medical University School Of Medicine
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Watanabe Takuo
Department Of Biochemistry And Molecular Vascular Biology Kanazawa University Graduate School Of Med
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Harada Shin-ichi
Center For Biomedical Research And Education School Of Medicine Kanazawa University
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Harada Shin-ichi
Dept. Biochem. Sch. Med. Kanazawa Univ.
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MUNESUE Seiichi
Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University
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Yamamoto Hiroshi
Department Of Energy Engineering And Science Nagoya University
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Yonekura Hideto
Kanazawa Medical Univ. School Of Medicine Uchinada Jpn
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Harada Shin-ichi
Center For Biomedical Research And Education Kanazawa University Graduate School Of Medical Science
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Munesue Seiichi
Department Of Biochemistry And Molecular Vascular Biology Kanazawa University Graduate School Of Med
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Yamamoto Hiroshi
Department Of Biochemistry And Molecular Vascular Biology Kanazawa University Graduate School Of Med
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Yamamoto Hiroshi
Departmemt Of Chemical Engineering University Of Tokyo
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