Expression of the human RNA-binding protein HuR in Trypanosoma brucei increases the abundance of mRNAs containing AU-rich regulatory elements

Nucleic Acids Res. 2002 Oct 15;30(20):4414-24. doi: 10.1093/nar/gkf577.

Abstract

The salivarian trypanosome Trypanosoma brucei infects mammals and is transmitted by tsetse flies. The mammalian 'bloodstream form' trypanosome has a variant surface glycoprotein coat and relies on glycolysis while the procyclic form from tsetse flies has EP protein on the surface and has a more developed mitochondrion. We show here that the mRNA for the procyclic-specific cytosolic phosphoglycerate kinase PGKB, like that for EP proteins, contains a regulatory AU-rich element (ARE) that destabilises the mRNA in bloodstream forms. The human HuR protein binds to, and stabilises, mammalian mRNAs containing AREs. Expression of HuR in bloodstream-form trypanosomes resulted in growth arrest and in stabilisation of the EP, PGKB and pyruvate, phosphate dikinase mRNAs, while three bloodstream-specific mRNAs were reduced in abundance. The synthesis and abundance of unregulated mRNAs and proteins were unaffected. Our results suggest that regulation of mRNA stability by AREs arose early in eukaryotic evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Adenine / analysis
  • Animals
  • Antigens, Surface*
  • Base Sequence
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Gene Expression Regulation, Developmental
  • Humans
  • Molecular Sequence Data
  • Phosphoglycerate Kinase / genetics
  • Phosphoglycerate Kinase / metabolism
  • Protozoan Proteins / biosynthesis
  • RNA Stability*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • RNA, Protozoan / chemistry
  • RNA, Protozoan / metabolism*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Trypanosoma brucei brucei / genetics*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosoma brucei brucei / metabolism
  • Uracil / analysis

Substances

  • 3' Untranslated Regions
  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Protozoan Proteins
  • RNA, Messenger
  • RNA, Protozoan
  • RNA-Binding Proteins
  • Uracil
  • Phosphoglycerate Kinase
  • Adenine