Single-locus targeting constructs for reliable regulated RNAi and transgene expression in Trypanosoma brucei

Mol Biochem Parasitol. 2008 Sep;161(1):76-9. doi: 10.1016/j.molbiopara.2008.05.006. Epub 2008 Jun 7.

Abstract

A major obstacle to reproducible expression of recombinant transcripts lies in the epigenetic effects of the flanking chromatin following integration. We previously presented a strategy to overcome this problem in bloodstream form Trypanosoma brucei, using a reporter to identify a ribosomal-spacer locus that supports optimal expression and then marking that locus for subsequent targeting. Advantages include elimination of variable-expression position-effects and the easy confirmation of correct integration. We now report a set of validated constructs that exploit this system for expression of dsRNA or recombinant protein. The current construct-set allows expression of intramolecular dsRNA for RNA interference knockdown or expression of proteins that can incorporate c-Myc epitope(s) or a fluorescent-tag for subcellular localisation, interaction and/or other functional analysis. The constructs are integrated at a single, marked locus and deliver reliable and reproducible expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression*
  • Gene Silencing*
  • Gene Targeting / methods*
  • RNA, Double-Stranded / biosynthesis
  • Recombinant Proteins / biosynthesis
  • Transgenes*
  • Trypanosoma brucei brucei / genetics*

Substances

  • RNA, Double-Stranded
  • Recombinant Proteins