期刊
GENOME BIOLOGY AND EVOLUTION
卷 5, 期 12, 页码 2420-2435出版社
OXFORD UNIV PRESS
DOI: 10.1093/gbe/evt188
关键词
RAGE; AGER; alternative splicing; mRNA isoforms; noncoding RNA; comparative genomics
资金
- Ministerio de Educacion y Ciencia [BFU2005-03683]
- Ministerio de Ciencia e Innovacion [BFU2008-03126]
- Comunidad de Madrid [GR/SAL/0670/2004, 200620M078]
- Fundacion Ramon Areces
- Universidad Autonoma de Madrid
- Ministerio de Educacion y Ciencia
- Comunidad de Madrid
- Programa Ramon y Cajal contract
- Amarouto (Comunidad Madrid-Fundacion Severo Ochoa) contract
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 transmembrane 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 seem to be species specific, especially the noncoding variants, with only two (canonical human Tv1-RAGE, and human N-truncated or Tv10-RAGE) conserved among the six different species. This could indicate a special evolution pattern of this gene at mRNA level.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据