Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex.
Journal: 2007/December - EMBO Journal
ISSN: 1460-2075
Abstract:
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.
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EMBO J 26(23): 4856-4866

Multifunctional class I transcription in <em>Trypanosoma brucei</em> depends on a novel protein complex

Supplementary Material

Supplementary Information

Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA
Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA
Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
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: ude.chcu@lznug
These authors contributed equally to this study
Present address: Pharmaceuticals Research Division, Roche, Basel CH-4052, Switzerland
Received 2007 Jun 25; Accepted 2007 Oct 9.

Abstract

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
Abstract
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Acknowledgments

We thank Miguel Navarro, Elizabeth Wirtz, and Stephen King for kindly providing the plasmid pMIG35, the plasmids pLew 115 and pLew 116, and the anti-LC8 antibody, respectively. We are also grateful to Mary Ann Gawinowicz (Protein Core Facility, Columbia University) for excellent mass spectrometric analysis. This work was supported by NIH grants AI059377 (AG), {"type":"entrez-nucleotide","attrs":{"text":"AI021729","term_id":"3237141","term_text":"AI021729"}}AI021729 (GAMC), and RR00862 (BTC).

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