Altered gamma-aminobutyric acid type B receptor subunit 1 splicing in alcoholics.
Altered gamma-aminobutyric acid type B receptor subunit 1 splicing in alcoholics.
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DOI：
10.1016/j.biopsych.2013.08.028
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发表时间：
2014-05-15
影响因子：
10.6
通讯作者：
Harris, R. Adron
中科院分区：
文献类型：
--
作者：
Lee, Changhoon;Mayfield, R. Dayne;Harris, R. Adron
慢性酒精暴露可改变剪接变异体的表达。γ-氨基丁酸B型（GABAB）受体经历剪接，是酒精中毒治疗的靶点，但关于酗酒者中该受体剪接变化的信息很少。我们研究了GABAB受体亚单位1（GABAB 1）在酒精性死后脑中的剪接。为了最大化GABAB 1剪接点鉴定，我们将基因特异性文库与RNA-seq相结合。剪接连接和映射读取也发现从内含子和基因间区域。我们比较了GABAB 1剪接点在前额叶皮层从14个酒精和15个对照组，并介绍了新的策略，每百万个独特的映射读段（RPJM）和每百万个映射读段（RPGM），每个剪接点模型的剪接酶读段和基因模型的剪接酶读段，用于定量剪接点和基因表达。新的剪接点检测表明，GABAB 1基因是至少两倍以上的长度比以前报道的基因。GABAB 1外显子和内含子RPGM数据显示在5'端外显子和外显子分组处低表达。这表明除了已知最长的主要转录物GABAB 1a之外，还有短剪接变体。我们发现，慢性酒精改变外显子/内含子的表达和剪接连接水平。γ-氨基丁酸（GABA）结合位点、跨膜区（TM）和微小RNA（miRNA）结合位点的表达减少可能会减少正常的GABAB 1转录物数量，从而减少酗酒者的正常信号转导。我们在人脑中发现了GABAB 1的新的复杂剪接，并表明长期饮酒会产生额外的剪接复杂性。
Chronic alcohol exposure can change splice variant expression. The gamma-aminobutyric acid type B (GABAB) receptor undergoes splicing and is an alcoholism treatment target, but there is little information about splicing changes in this receptor in alcoholics. We studied GABAB receptor subunit 1 (GABAB1) splicing in alcoholic postmortem brains. To maximize GABAB1 splice junction identification, we combined gene specific libraries with RNA-seq. Splice junctions and mapped reads were also found from intronic and intergenic regions. We compared GABAB1 splice junctions in prefrontal cortices from 14 alcoholic and 15 control subjects and introduced new strategies, reads per kilobase of splice junction model per million uniquely mapped reads (RPJM) and reads per kilobase of gene model per million mapped reads (RPGM), for quantitating splice junction and gene expression. Novel splice junction detection indicated that the GABAB1 gene is at least two times longer than the previously reported gene length. GABAB1 exon and intron RPGM data showed low expression at the 5’ end exons and exon grouping. This indicated that there are short splicing variants in addition to GABAB1a, the longest known major transcript. We found that chronic alcohol altered exon/intron expression and splice junction levels. Decreased expression of the gamma-aminobutyric acid (GABA) binding site, a transmembrane region (TM), and a microRNA (miRNA) binding site may decrease normal GABAB1 transcript population and thereby decrease normal signal transduction in alcoholics. We discovered novel, complex splicing of GABAB1 in human brain and showed that chronic alcohol produces additional splicing complexity.
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影响因子：
4.5
作者：
Pickrell JK;Pai AA;Gilad Y;Pritchard JK
通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
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影响因子：
48
作者：
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通讯作者：
Grimmond, Sean M.
影响因子：
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作者：
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DOI：
10.1006/bbrc.1998.9706
发表时间：
1998-12-09
影响因子：
3.1
作者：
Isomoto, S;Kaibara, M;Taniyama, K
通讯作者：
Taniyama, K