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  • The EMBO Journal (2007) 26, 4856 - 4866
  • doi:10.1038/sj.emboj.7601905

Published online: 1 November 2007

Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex

Jens Brandenburg1,a, Bernd Schimanski1,a, Everson Nogoceke2,b, Tu N Nguyen1, Júlio C Padovan3, Brian T Chait3, George AM Cross2 and Arthur Günzl1,4

  1. Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA
  2. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA
  3. Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA
  4. Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA

Correspondence to:

Arthur Günzl, Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3710, USA. Tel.: +1 860 679 8878; Fax: +1 860 679 8130; E-mail: gunzl@uchc.edu

aThese authors contributed equally to this study

bPresent address: Pharmaceuticals Research Division, Roche, Basel CH-4052, Switzerland

Received 25 June 2007; Accepted 9 October 2007

The vector-borne, protistan parasite Trypanosoma brucei is the only known eukaryote with a multifunctional RNA polymerase I that, in addition to ribosomal genes, transcribes genes encoding the parasite's major cell-surface proteins—the variant surface glycoprotein (VSG) and procyclin. In the mammalian bloodstream, antigenic variation of the VSG coat is the parasite's means to evade the immune response, while procyclin is necessary for effective establishment of trypanosome infection in the fly. Moreover, the exceptionally high efficiency of mono-allelic VSG expression is essential to bloodstream trypanosomes since its silencing caused rapid cell-cycle arrest in vitro and clearance of parasites from infected mice. Here we describe a novel protein complex that recognizes class I promoters and is indispensable for class I transcription; it consists of a dynein light chain and six polypeptides that are conserved only among trypanosomatid parasites. In accordance with an essential transcriptional function of the complex, silencing the expression of a key subunit was lethal to bloodstream trypanosomes and specifically affected the abundance of rRNA and VSG mRNA. The complex was dubbed class I transcription factor A.

  • Keywords:

    • class I transcription factor,
    • DYNLL1,
    • procyclin,
    • Tryponosoma brucei,
    • VSG