Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing

Michèle Rouleau, Alan Tourancheau, Camille Girard-Bock, Lyne Villeneuve, Jonathan Vaucher, Anne Marie Duperré, Yannick Audet-Delage, Isabelle Gilbert, Ion Popa, Arnaud Droit, Chantal Guillemette

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalCell Reports
Volume17
Issue number1
DOIs
StatePublished - 27 Sep 2016
Externally publishedYes

Keywords

  • Glucuronosyltransferase (UGT)
  • RNA sequencing
  • alternative splicing
  • cell metabolism
  • drug metabolism
  • glucuronidation
  • transcriptome

Fingerprint

Dive into the research topics of 'Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing'. Together they form a unique fingerprint.

Cite this