Tourancheau A, Margaillan G, Rouleau M, Gilbert I, Villeneuve L, Lévesque E, Droit A, Guillemette C
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.
Faculty of Pharmacy, Laval University, Québec, QC, Canada.
Pharmacogenomics J. 2016 Feb;16(1):60-70. doi: 10.1038/tpj.2015.20. Epub 2015 Apr 14.
A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a prerequisite to the establishment of an individual's UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the 10 human UGT gene loci in normal and tumoral metabolic tissues by targeted RNA next-generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGT expression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases.
全面了解人类尿苷二磷酸葡萄糖醛酸基转移酶（UGT）转录组是建立个体UGT代谢葡萄糖醛酸化特征的先决条件。在这里，我们通过靶向RNA下一代测序揭示了正常和肿瘤代谢组织中10个人类UGT基因座的转录组图谱。与人类hg19参考基因组比对识别出234个新的外显子-外显子连接。我们找回了所有先前已知的UGT1和UGT2酶编码转录本，并鉴定出130多个结构和功能多样的新UGT变体。我们进一步揭示了UGT基因座的修订基因组结构，并为每个UGT基因提供了全面的转录本清单。数据还揭示了UGT转录组以组织和肿瘤特异性方式发生的重塑。调节UGT表达和蛋白质功能的复杂可变剪接程序可能在决定器官的解毒能力和应激相关反应中起关键作用，对药物反应和疾病有重大影响。
