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Regulation of alternative splicing of the receptor for advanced glycation endproducts (RAGE) through G-rich cis-elements and heterogenous nuclear ribonucleoprotein H
- Source :
- Journal of Biochemistry. 147(5):651-659
- Publication Year :
- 2010
- Publisher :
- Oxford University Press / Japanese Biochemical Society = 日本生化学会, 2010.
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Abstract
- 金沢大学医薬保健研究域医学系<br />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.
- Subjects :
- Receptor for Advanced Glycation End Products
Biology
Regulatory Sequences, Ribonucleic Acid
Biochemistry
receptor for advanced glycation endproducts (RAGE)
Heterogeneous-Nuclear Ribonucleoproteins
G-stretch
heterogenous nuclear ribonucleoprotein (hnRNP) H
Cell Line
Exon
alternative splicing
Humans
Receptors, Immunologic
Receptor
Molecular Biology
Ribonucleoprotein
Reverse Transcriptase Polymerase Chain Reaction
Alternative splicing
Intron
RNA
Endothelial Cells
General Medicine
Exons
Molecular biology
Cell biology
GC Rich Sequence
endogenous secretory RAGE (esRAGE)
Decoy
Minigene
Subjects
Details
- Language :
- English
- ISSN :
- 0021924X
- Volume :
- 147
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of Biochemistry
- Accession number :
- edsair.doi.dedup.....1993a641ced95fb4f8dfaf1bd5f7eeb5