Quantitative profiling of the UGT transcriptome in human drug metabolizing tissues [Total RNA]

Purpose: Maintenance of cellular homeostasis and xenobiotics detoxification relies on the glucuronidation pathway mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by 10 highly homologous genes. Recent evidence suggests that alternative splicing largely expands the human UGT transcriptome. Results: we establish the quantitative portrait of the UGT transcriptome in major metabolic organs. RNA sequencing uncovered that AS significantly shapes the UGT transcriptome, with variants quantitatively representing up to 35% and 60% UGT transcripts in normal and tumoral tissues respectively. Novel distinctive in-frame sequences were present in 20% alternative transcripts, which potentially encode UGT isoforms with distinct structural and functional features. Conclusions: This work exposes the important quantitative and biological significance of alternative UGT expression likely creating unparalleled protein diversity evolving from enzymes to regulators of cell metabolism. Total RNA was extracted from liver, kidney, intestine and colon from multiple human donors. RNA-sequencing was conducted with a Illumina HiSeq 2500 system