Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha
Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha
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DOI：
10.1194/jlr.m500157-jlr200
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发表时间：
2005-12-01
影响因子：
6.5
通讯作者：
Tontonoz, P
中科院分区：
文献类型：
--
作者：
Chen, MY;Beaven, S;Tontonoz, P
肝X受体α(LXRα)是核激素受体超家族中的一员，在脂质稳态中起着重要作用。在这里，我们描述了两种可供选择的人类LXRα转录本，命名为LXRα2和LXRα3。这三种LXRα亚型都是通过选择性剪接和差异启动子使用来自同一基因。LXRα2亚型缺乏LXRα1的前45个氨基酸，是通过使用新的启动子和第一外显子产生的。LXRα3在配体结合区缺乏50个氨基酸，是通过交替识别外显子6的3‘-剪接位点而产生的。LXRα2和LXRα3在大多数组织中的表达水平低于LXRα1，但LXRα2在睾丸中的表达占主导地位。LXRα2和LXRα3都与维甲酸X受体异源二聚，并与LXR反应元件结合。与LXRα1相比，LXRα2的转录活性降低，表明LXRα的N末端结构域对其完整的转录活性是必不可少的。LXRα3不能结合配体，在转录上是不活跃的。这些观察结果概述了先前未知的N端在LXR功能中的作用，并表明在某些生物背景下替代LXRα转录本的表达可能会影响LXR信号和脂质代谢。作者声明：by J.人肝X受体α两个选择性剪接转录变异体的鉴定和鉴定。
The liver X receptor alpha ( LXR alpha) is a member of the nuclear hormone receptor superfamily that plays an important role in lipid homeostasis. Here we characterize two alternative human LXR alpha transcripts, designated LXR alpha 2 and LXR alpha 3. All three LXR alpha isoforms are derived from the same gene via alternative splicing and differential promoter usage. The LXR alpha 2 isoform lacks the first 45 amino acids of LXR alpha 1, and is generated through the use of a novel promoter and first exon. LXR alpha 3 lacks 50 amino acids within the ligand binding domain and is generated through alternative recognition of the 3 ' - splice site in exon 6. LXR alpha 2 and LXR alpha 3 are expressed at lower levels compared with LXR alpha 1 in most tissues, except that LXR alpha 2 expression is dominant in testis. Both LXR alpha 2 and LXR alpha 3 heterodimerize with the retinoid X receptor and bind to LXR response elements. LXR alpha 2 shows reduced transcriptional activity relative to LXR alpha 1, indicating that the N- terminal domain of LXR alpha is essential for its full transcriptional activity. LXR alpha 3 is unable to bind ligand and is transcriptionally inactive. These observations outline a previously unrecognized role for the N terminus in LXR function and suggest that the expression of alternative LXR alpha transcripts in certain biological contexts may impact LXR signaling and lipid metabolism. Chen, M., S. Beaven, and P. Tontonoz. Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha.