title: Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing.
abstract: 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.
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: A
authors: A
authors: Tourancheau
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: G
authors: G
authors: Margaillan
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: M
authors: M
authors: Rouleau
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: I
authors: I
authors: Gilbert
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: L
authors: L
authors: Villeneuve
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Medicine, Laval University, Québec, QC, Canada.
authors: E
authors: E
authors: Lévesque
authors: Faculty of Medicine, Laval University, Québec, QC, Canada.
authors: A
authors: A
authors: Droit
authors: Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Québec, QC, Canada.|Faculty of Pharmacy, Laval University, Québec, QC, Canada.|Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, CHU de Quebec Research Center, Quebec, QC, Canada.
authors: C
authors: C
authors: Guillemette
mesh_terms: D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology; D004717:Endometrium / Q000201:enzymology; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007414:Intestinal Neoplasms / Q000201:enzymology; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology; D008297:Male; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D009928:Organ Specificity; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome; D014594:Uterine Neoplasms / Q000201:enzymology
chemical_list: D012333:RNA, Messenger; D014453:Glucuronosyltransferase