Expression and regulation of multiple murine ATP-binding cassette transporter G1 mRNAs/isoforms that stimulate cellular cholesterol efflux to high density lipoprotein
Expression and regulation of multiple murine ATP-binding cassette transporter G1 mRNAs/isoforms that stimulate cellular cholesterol efflux to high density lipoprotein
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DOI：
10.1074/jbc.m408652200
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发表时间：
2004-10-29
影响因子：
4.8
通讯作者：
Edwards, PA
中科院分区：
文献类型：
--
作者：
Nakamura, K;Kennedy, MA;Edwards, PA
据报道，鼠Abcg 1基因由15个外显子组成，编码单个mRNA（本文称为Abcg 1-a）和蛋白质。我们现在证明，（i）鼠基因包含两个额外的编码外显子下游的外显子1，（ii）转录涉及使用多个启动子，和（iii）RNA进行选择性剪接反应。结果，表达了三种mRNA，其编码三种推定的蛋白质同种型，其氨基末端不同。ABCG 1转录本在体内多种组织中响应于肝脏X受体配体T0901317而被诱导。在外显子2的内含子下游的四个肝X受体反应元件的鉴定和表征提供了这种诱导发生的机制。重要的是，胆固醇流出到高密度脂蛋白刺激Hek 293细胞与编码个别ABCG 1亚型的质粒转染。在胚胎11.5-15.5天的小鼠胚胎中的原位杂交研究显示，在嗅上皮、后脑、眼睛和背根神经节中强烈表达ABCG 1转录本。在神经元组织和眼睛中相对高水平的表达表明，ABCG 1依赖性胆固醇流出可能是至关重要的正常神经元功能，除了其在巨噬细胞中的作用。
The murine Abcg1 gene is reported to consist of 15 exons that encode a single mRNA ( herein referred to as Abcg1-a) and protein. We now demonstrate that (i) the murine gene contains two additional coding exons downstream of exon 1, (ii) transcription involves the use of multiple promoters, and (iii) the RNA undergoes alternative splicing reactions. As a result, three mRNAs are expressed that encode three putative protein isoforms that differ at their amino terminus. ABCG1 transcripts are induced in vivo in multiple tissues in response to the liver X receptor ligand T0901317. Identification and characterization of four liver X receptor response elements in the intron downstream of exon 2 provides a mechanism by which this induction occurs. Importantly, cholesterol efflux to high density lipoprotein was stimulated following transfection of Hek293 cells with plasmids encoding individual ABCG1 isoforms. In situ hybridization studies in embryonic day 11.5-15.5 mouse embryos revealed strong expression of ABCG1 transcripts in the olfactory epithelium, hind brain, eye, and dorsal root ganglia. The relatively high levels of expression in neuronal tissues and the eye suggest that ABCG1-dependent cholesterol efflux may be critical for normal neuronal function in addition to its role in macrophages.