Expression of mRNA transcripts encoding membrane transporters detected with whole transcriptome sequencing of human brain and liver.

ABSTRACT

BACKGROUND: Membrane transporters control the influx and efflux of endogenous and xenobiotic substrates, including nutrients and drugs, across cellular membranes. OBJECTIVE: Whole transcriptome sequencing enables simultaneous analysis of overall and allele-specific mRNA expression, and the detection of multiple RNA isoforms. METHODS: 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. RESULTS: 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. CONCLUSION: 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.