Mouse Specific Cleavage-Resistant RAGE Splice Variant
| Autor: | Stefania, Di Maggio, Elena, Gatti, Jaron, Liu, Matteo, Bertolotti, Günter, Fritz, Marco E, Bianchi, Angela, Raucci |
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| Rok vydání: | 2015 |
| Předmět: |
Primates
Lung Development endocrine system diseases Physiology Organogenesis Mouse Models Molting Research and Analysis Methods Rodents Biochemistry Model Organisms Sequence Motif Analysis Medicine and Health Sciences Animals cardiovascular diseases Molecular Biology Techniques Sequencing Techniques Molecular Biology Mammals Organisms nutritional and metabolic diseases Biology and Life Sciences Proteins Heart Animal Models Proteases Enzymes Vertebrates Amniotes cardiovascular system Cardiovascular Anatomy Enzymology Anatomy Physiological Processes human activities Sequence Analysis Organism Development Research Article Developmental Biology |
| Zdroj: | PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The receptor for advanced glycation end-products (RAGE) is involved in the onset and progression of several inflammatory diseases. The RAGE primary transcript undergoes numerous alternative splicing (AS) events, some of which are species-specific. Here, we characterize the mouse-specific mRAGE_v4 splice variant, which is conserved in rodents and absent in primates. mRAGE_v4 derives from exon 9 skipping and encodes a receptor (M-RAGE) that lacks 9 amino acids between the transmembrane and the immunoglobulin (Ig) domains. RNA-Seq data confirm that in mouse lung mRAGE_v4 is the most abundant RAGE mRNA isoform after mRAGE, which codes for full-length RAGE (FL-RAGE), while in heart all RAGE variants are almost undetectable. The proteins M-RAGE and FL-RAGE are roughly equally abundant in mouse lung. Contrary to FL-RAGE, M-RAGE is extremely resistant to shedding because it lacks the peptide motif recognized by both ADAM10 and MMP9, and does not contribute significantly to soluble cRAGE formation. Thus, a cassette exon in RAGE corresponds to a specific function of the RAGE protein–the ability to be shed. Given the differences in RAGE AS variants between rodents and humans, caution is due in the interpretation of results obtained in mouse models of RAGE-dependent human pathologies. |
| Databáze: | OpenAIRE |
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