IRF5公司
外显子
干扰素调节因子
生物
选择性拼接
遗传学
发起人
信使核糖核酸
等位基因
单核苷酸多态性
RNA剪接
分子生物学
转录因子
基因
核糖核酸
基因表达
基因型
作者
N ClarkDaniel,P LambertJared,E TillRodney,Lissenya B. Argueta,E GreenhalghKathryn,HenrieBrandon,BillsTrieste,F HawkleyTyson,G RoznikMarinya,M SloanJason,MayhewVera,WoodlandLoc,P NelsonEric,TsaiMeng-Hsuan,Brian Poole
出处
期刊:Journal of Interferon and Cytokine Research
[Mary Ann Liebert]
日期:2014-05-01
卷期号:34 (5): 354-365
被引量:6
标识
DOI:10.1089/jir.2012.0105
摘要
The rs2004640 single nucleotide polymorphism and the CGGGG copy-number variant (rs77571059) are promoter polymorphisms within interferon regulatory factor 5 (IRF5). They have been implicated as susceptibility factors for several autoimmune diseases. IRF5 uses alternative promoter splicing, where any of 4 first exons begin the mRNA. The CGGGG indel is in exon 1A's promoter; the rs2004640 allele creates a splicing recognition site, enabling usage of exon 1B. This study aimed at characterizing alterations in IRF5 mRNA due to these polymorphisms. Cells with risk polymorphisms exhibited ~2-fold higher levels of IRF5 mRNA and protein, but demonstrated no change in mRNA stability. Quantitative PCR demonstrated decreased usage of exons 1C and 1D in cell lines with the risk polymorphisms. RNA folding analysis revealed a hairpin in exon 1B; mutational analysis showed that the hairpin shape decreased translation 5-fold. Although translation of mRNA that uses exon 1B is low due to a hairpin, increased IRF5 mRNA levels in individuals with the rs2004640 risk allele lead to higher overall protein expression. In addition, several new splice variants of IRF5 were sequenced. IRF5's promoter polymorphisms alter first exon usage and increase transcription levels. High levels of IRF5 may bias the immune system toward autoimmunity.
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