MxA transcripts with distinct first exons and modulation of gene expression levels by single-nucleotide polymorphisms in human bronchial epithelial cells.

MxA transcripts with distinct first exons and modulation of gene expression levels by single-nucleotide polymorphisms in human bronchial epithelial cells.
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DOI:
10.1007/s00251-012-0663-8
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发表时间:
2013-03
期刊:
影响因子:
3.2
通讯作者:
Keicho N
Keicho N
中科院分区:
医学4区
文献类型:
--
作者:
Noguchi S;Hijikata M;Hamano E;Matsushita I;Ito H;Ohashi J;Nagase T;Keicho N

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黏液病毒抗性A (MxA)是干扰素(IFN)诱导的主要抗病毒蛋白。ifn刺激反应元件(ISRE)附近MxA的启动子单核苷酸多态性(snp)经常与各种病毒性疾病相关,包括新发呼吸道感染。我们研究了人支气管上皮细胞中具有不同第一外显子的MxA转录本的表达谱。原代培养时,从不同基因型的肺组织中分离支气管上皮,实时逆转录聚合酶链反应总RNA。鉴定了先前报道的MxA转录本(T1)和最近注册的具有不同5 '第一外显子(T0)的转录本。IFN-β和多肌苷-多胞酸诱导T1转录本的表达量比T0高约100倍,T0转录本在其转录起始位点附近也有一个潜在的ISRE基序。即使没有诱导剂,T1转录本也占MxA总表达量的约三分之二,其水平与其启动子和外显子1 snp (rs17000900、rs2071430和rs464138)显著相关。我们的研究结果表明,在呼吸道病毒感染中观察到的MxA可能由T1转录本主导,部分受相关5 ' snp的影响。本文的在线版本(doi:10.1007/s00251-012-0663-8)包含补充材料,授权用户可使用。
Myxovirus resistance A (MxA) is a major interferon (IFN)-inducible antiviral protein. Promoter single-nucleotide polymorphisms (SNPs) of MxA near the IFN-stimulated response element (ISRE) have been frequently associated with various viral diseases, including emerging respiratory infections. We investigated the expression profile of MxA transcripts with distinct first exons in human bronchial epithelial cells. For primary culture, the bronchial epithelium was isolated from lung tissues with different genotypes, and total RNA was subjected to real-time reverse transcription polymerase chain reaction. The previously reported MxA transcript (T1) and a recently registered transcript with a distinct 5′ first exon (T0) were identified. IFN-β and polyinosinic–polycytidylic acid induced approximately 100-fold higher expression of the T1 transcript than that of the T0 transcript, which also had a potential ISRE motif near its transcription start site. Even without inducers, the T1 transcript accounted for approximately two thirds of the total expression of MxA, levels of which were significantly associated with its promoter and exon 1 SNPs (rs17000900, rs2071430, and rs464138). Our results suggest that MxA observed in respiratory viral infections is possibly dominated by the T1 transcript and partly influenced by relevant 5′ SNPs. The online version of this article (doi:10.1007/s00251-012-0663-8) contains supplementary material, which is available to authorized users.
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