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Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing

2016-09-27 12:38:55

Gene; 27 September 2016: DOI:10.1016/j.celrep.2016.08.077

Michèle Rouleau, Alan Tourancheau, Camille Girard-Bock, Lyne Villeneuve, Jonathan Vaucher, Anne-Marie Duperré, Yannick Audet-Delage, Isabelle Gilbert, Ion Popa, Arnaud Droit, Chantal Guillemette4,correspondencePress enter key for correspondence informationemail



Abstract


Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features. Follow-up cell-based assays reveal biological functions for these alternative UGT proteins. Some isoforms were found to inhibit or induce inactivation of drugs and steroids in addition to perturbing global cell metabolism (energy, amino acids, nucleotides), cell adhesion, and proliferation. This work highlights the biological relevance of alternative UGT expression, which we propose increases protein diversity through the evolution of metabolic regulators from specific enzymes.



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Empire Genomic's IDetect SuperStain horseradish peroxidase (HRP) polymer kit was used in this publication




Key Words

Glucuronosyl transferase (UGT) | glucuronidation | drug metabolism | cell metabolism | RNA sequencing | alternative splicing | transcriptome