Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex.
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.
Brandenburg
Jens
J
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030-3710, USA.
Schimanski
Bernd
B
Nogoceke
Everson
E
Nguyen
Tu N
TN
Padovan
Júlio C
JC
Chait
Brian T
BT
Cross
George A M
GA
Günzl
Arthur
A
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004398:Dyneins; D020868:Gene Silencing; D017125:Genes, Protozoan; D005822:Genetic Vectors; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D015800:Protozoan Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000737:chemistry* / Q000378:metabolism
D002352:Carrier Proteins; D016213:Cyclins; D029721:Drosophila Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014643:Variant Surface Glycoproteins, Trypanosoma; D004398:Dyneins