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The Mouse-Specific Splice Variant mRAGE_v4 Encodes a Membrane-Bound RAGE That Is Resistant to Shedding and Does Not Contribute to the Production of Soluble RAGE

Di Maggio, Stefania ; Gatti, Elena ; Liu, Jaron ; Bertolotti, Matteo ; Fritz, Günter ; Bianchi, Marco E ; Raucci, Angela Fukai, Tohru

PloS one, 2016-09, Vol.11 (9), p.e0153832-e0153832 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
The Mouse-Specific Splice Variant mRAGE_v4 Encodes a Membrane-Bound RAGE That Is Resistant to Shedding and Does Not Contribute to the Production of Soluble RAGE
Autor: Di Maggio, Stefania ; Gatti, Elena ; Liu, Jaron ; Bertolotti, Matteo ; Fritz, Günter ; Bianchi, Marco E ; Raucci, Angela
Fukai, Tohru
Assuntos: Advanced glycosylation end products ; Aging ; Alternative splicing ; Amino acids ; Animal models ; Biology ; Biology and Life Sciences ; Cell adhesion & migration ; Gelatinase B ; Genetics ; Glycosylation ; Immunoglobulins ; Inflammatory diseases ; Kinases ; Ligands ; Lungs ; Medicine and Health Sciences ; Oncology ; Physiology ; Primates ; Protection and preservation ; Proteins ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; RNA sequencing ; Rodents ; Shedding ; Transcription ; Trends
É parte de: PloS one, 2016-09, Vol.11 (9), p.e0153832-e0153832
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
These authors also contributed equally to this work.
Conceived and designed the experiments: EG MEB AR.Performed the experiments: SDM EG JL GF MB.Analyzed the data: SDM EG JL GF MEB AR.Contributed reagents/materials/analysis tools: GF MEB AR.Wrote the paper: EG GF MEB AR.
Current address: A*STAR Institute of Medical Biology, 8A Biomedical Grove, Immunos #06-18A, Singapore, 138648, Singapore
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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The Mouse-Specific Splice Variant mRAGE_v4 Encodes a Membrane-Bound RAGE That Is Resistant to Shedding and Does Not Contribute to the Production of Soluble RAGE

Di Maggio, Stefania ; Gatti, Elena ; Liu, Jaron ; Bertolotti, Matteo ; Fritz, Günter ; Bianchi, Marco E ; Raucci, Angela Fukai, Tohru

United States: Public Library of Science

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