Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Pharmacogenet Genomics. 2013 May;23(5):269-78. doi: 10.1097/FPC.0b013e32835ff536.
Membrane transporters control the influx and efflux of endogenous and xenobiotic substrates, including nutrients and drugs, across cellular membranes.
Whole transcriptome sequencing enables simultaneous analysis of overall and allele-specific mRNA expression, and the detection of multiple RNA isoforms.
Here we characterize variation in RNA transcripts emanating from gene loci encoding transporters based on RNAseq data from 10 human brains (including cocaine overdose and normal brain tissues) and 12 normal livers.
mRNA expression was detected in 65% of transporter genes in either tissue, with many genes generating multiple mRNA transcripts. Single-nucleotide polymorphisms within transporters with previous evidence for pharmacogenomics impact were detected. We also identified noncoding RNAs in the vicinity of transporter genes with potential regulatory functions.
The results obtained with RNAseq provide detailed information on transporter mRNA expression at the molecular level, affording new avenues for the study of membrane transport, with relevance to drug efficacy and toxicity.
膜转运蛋白控制内源性和外源性底物(包括营养物和药物)穿过细胞膜的流入和流出。
全转录组测序能够同时分析整体和等位基因特异性 mRNA 表达,并检测多种 RNA 异构体。
在这里,我们根据来自 10 个人脑(包括可卡因过量和正常脑组织)和 12 个正常肝脏的 RNAseq 数据,对编码转运蛋白的基因座产生的 RNA 转录本的变异进行了描述。
在两种组织中的 65%的转运蛋白基因中检测到了 mRNA 表达,许多基因产生了多个 mRNA 转录本。在具有先前药物基因组学影响证据的转运蛋白内检测到了单核苷酸多态性。我们还在转运蛋白基因附近鉴定了具有潜在调控功能的非编码 RNA。
RNAseq 获得的结果提供了在分子水平上关于转运蛋白 mRNA 表达的详细信息,为膜转运的研究开辟了新途径,与药物疗效和毒性相关。