Quantitative profiling of the UGT transcriptome in human drug-metabolizing tissues.

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodeling in favor of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome.

• Autores: Tourancheau, A; Rouleau, M; Guauque Olarte, Sandra Milena; Villeneuve, L; Gilbert, I; Droit, A; Guillemette, C
• Tipo de recurso: Article of journal
• Fecha de publicación: 2018
• Institución: Universidad Cooperativa de Colombia
• Repositorio: Repositorio UCC
• OAI Identifier: oai:repository.ucc.edu.co:20.500.12494/41678
• Acceso en línea: https://doi.org/10.14349/rlp.2019.v51.n3.1; https://hdl.handle.net/20.500.12494/41678
• Palabra clave: glucuronosyltransferase; proteome; transcriptome; drug; glucuronosyltransferase; transcriptome; UGT1A1 enzyme; UGT2A1 protein; human; alternative RNA splicing; Article; carcinogenesis; controlled study; drug clearance; drug metabolism; drug response; female; gene; gene expression profiling; gene expression regulation; genetic variability; human; human tissue; interindividual variability; male; priority journal; RNA sequence; UGT gene; UGT1 gene; UGT2 gene; drug effect; genetics; metabolic clearance rate; metabolism; pharmacogenetic variant; physiology; procedures; tissue distribution; Gene Expression Profiling; Glucuronosyltransferase; Humans; Metabolic Clearance Rate; Pharmaceutical Preparations; Pharmacogenomic Variants; Tissue Distribution; Transcriptome
• Rights: closedAccess
• License: http://purl.org/coar/access_right/c_14cb