Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency.
Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency.
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DOI：
10.1186/s12967-015-0585-y
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发表时间：
2015-07-04
影响因子：
7.4
通讯作者：
Martinez-Delgado B
中科院分区：
文献类型：
--
作者：
Matamala N;Martínez MT;Lara B;Pérez L;Vázquez I;Jimenez A;Barquín M;Ferrarotti I;Blanco I;Janciauskiene S;Martinez-Delgado B
SERPINA1 是 α-1 抗胰蛋白酶 (AAT) 的基因，AAT 是一种具有抗蛋白酶和免疫调节活性的急性期蛋白。 SERPINA1 基因突变会导致 AAT 缺乏，并使个体易患早发性肺气肿和肝脏疾病。 SERPINA1 基因的表达受不同启动子和非编码外显子 1A、1B 和 1C 之间的选择性剪接事件的调节。我们开发了三种定量 PCR (QT-PCR) 检测（1A、1B 和 1C）。这些测定法用于分析以下组织中的 SERPINA1 替代转录物：(1) 16 个人体组织和 (2) 来自 33 名具有 AAT 突变的受试者和 7 名对照者的外周血白细胞。发现 SERPINA1 转录本具有组织特异性表达。 1A 转录本主要在白细胞和肺组织中表达，而 1B 测定检测到的转录本高度局限于白细胞。只有 1B 转录本与血清 AAT 水平显着相关。 1C 转录本特别存在于肺、肝、肾和胰腺中。此外，转录本的表达与AAT基因型相关。虽然 AAT 缺陷变体对转录本表达没有明显影响，但无效等位基因与不同转录本的显着减少相关。区分 SERPINA1 选择性剪接产物的可能性将有助于我们更好地了解 SERPINA1 基因的调控及其与 SERPINA1 突变相关疾病的关联。本文的在线版本 (doi:10.1186/s12967-015-0585-y) 包含补充材料，可供授权用户使用。
SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C. We have developed three quantitative PCR (QT-PCR) assays (1A, 1B and 1C). These assays were applied for the analysis of SERPINA1 alternative transcripts in: (1) 16 human tissues and (2) peripheral blood leukocytes from 33 subjects with AAT mutations and 7 controls. Tissue-specific expression was found for the SERPINA1 transcripts. The 1A transcripts were mainly expressed in leukocytes and lung tissue while those detected with the 1B assay were highly restricted to leukocytes. Only 1B transcripts significantly correlated with serum AAT levels. The 1C transcripts were specifically found in lung, liver, kidney and pancreas. Furthermore, the expression of transcripts was related to AAT genotypes. While deficient variants of AAT had no pronounced effect on the transcript expression, null alleles were associated with significant reduction of different transcripts. The possibility to discriminate between SERPINA1 alternative splicing products will help us to understand better the regulation of SERPINA1 gene and its association with SERPINA1 mutations-related diseases. The online version of this article (doi:10.1186/s12967-015-0585-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1164/ajrccm.157.1.9702033
发表时间：
1998-01-01
影响因子：
24.7
作者：
Knoell, DL;Ralston, DR;Wewers, MD
通讯作者：
Wewers, MD
DOI：
10.1038/nrm3454
发表时间：
2012-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Modrek, B;Resch, A;Lee, C
通讯作者：
Lee, C
影响因子：
15.9
作者：
Lomas, DA;Mahadeva, R
通讯作者：
Mahadeva, R
影响因子：
3.8
作者：
Lee, J;Novoradovskaya, N;Brantly, M
通讯作者：
Brantly, M