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

被引:53
作者
Brandenburg, Jens
Schimanski, Bernd
Nogoceke, Everson
Nguyen, Tu N.
Padovan, Julio C.
Chait, Brian T.
Cross, George A. M.
Guenzl, Arthur
机构
[1] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA
[2] Rockefeller Univ, Mol Parasitol Lab, New York, NY 10021 USA
[3] Rockefeller Univ, Lab Mass Spectrom & Gaseous Ion Chem, New York, NY 10021 USA
[4] Univ Connecticut, Dept Mol Microbiol & Struct Biol, Farmington, CT USA
[5] Div Pharmaceut Res, CH-4052 Basel, Switzerland
关键词
class I transcription factor; DYNLL1; procyclin; Tryponosoma brucei; VSG;
D O I
10.1038/sj.emboj.7601905
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4856 / 4866
页数:11
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