Complex tissue-specific patterns and distribution of multiple RAGE splice variants in different mammals
Entity
UAM. Departamento de Biología MolecularPublisher
Oxford University PressDate
2013-12-01Citation
10.1093/gbe/evt188
Genome Biology and Evolution 5.12 (2013): 2420-2435
ISSN
1759-6653DOI
10.1093/gbe/evt188Funded by
This work was supported by grants from the Ministerio de Educación y Ciencia (BFU2005-03683), Ministerio de Ciencia e Innovación (BFU2008-03126), Comunidad de Madrid (GR/SAL/0670/ 2004, and 200620M078), Fundación Ramón Areces. R.L.-D. held a postgraduate fellowship from the Universidad Autónoma de Madrid, A.R. held a postgraduate fellowship (FPU) from the Ministerio de Educación y Ciencia, O.V. held a postgraduate fellowship (FPI) from the Comunidad de Madrid, and B.A. held a Programa Ramón y Cajal contract and an Amarouto (Comunidad Madrid-Fundación Severo Ochoa) contract. The CBMSO receives an institutional grant from Fundación Ramón ArecesEditor's Version
http://dx.doi.org/10.1093/gbe/evt188Subjects
AGER; Alternative splicing; Comparative genomics; mRNA isoforms; Noncoding RNA; RAGE; Biología y Biomedicina / BiologíaRights
© The Author(s) 2013Abstract
The receptor for advanced glycosylation end products (RAGE) is a multiligand receptor involved in diverse cell signaling pathways. Previous studies show that this gene expresses several splice variants in human, mouse, and dog. Alternative splicing (AS) plays an important role in expanding transcriptomic and proteomic diversity, and it has been related to disease. AS is also one of the main evolutionary mechanisms in mammalian genomes. However, limited information is available regarding the AS of RAGE in a wide context of mammalian tissues. In this study, we examined in detail the different RAGE mRNAs generated by AS from six mammals, including two primates (human and monkey), two artiodactyla (cow and pig), and two rodentia (mouse and rat) in 6-18 different tissues including fetal, adult, and tumor. By nested reverse transcription-polymerase chain reaction (RT-PCR) we identified a high number of splice variants including noncoding transcripts and predicted coding ones with different potential protein modifications affecting mainly the trans membrane and ligand-binding domains that could influence their biological function. However, analysis of RNA-seq data enabled detecting only the most abundant splice variants.More than 80%of the detected RT-PCR variants (87 of 101 transcripts) are novel (different exon/intron structure to the previously described ones), and interestingly, 20-60% of the total transcripts (depending on the species) are noncoding ones that present tissue specificity. Our results suggest that RAGE undergoes extensive AS in mammals, with different expression patterns among adult, fetal, and tumor tissues. Moreover, most splice variants seemto be species specific, especially the noncoding variants, with only two(canonical human Tv1-RAGE, and humanN-truncated or Tv10-RAGE) conserved among the six different species. This could indicate a special evolution pattern of this gene at mRNA level
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Google Scholar:López-Díez, Raquel
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Rastrojo, Alberto
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Villate, Olatz
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Aguado, Begoña
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