the cell cycle regulated transcriptome of trypanosoma brucei细胞周期调控转录组的锥虫属brucei.pdfVIP

The Cell Cycle Regulated Transcriptome of Trypanosoma brucei 1 1 2 1 Stuart K. Archer *, Diana Inchaustegui , Rafael Queiroz , Christine Clayton ¨ 1 Zentrum fur Molekulare Biologie Heidelberg, DKFZ-ZMBH Allianz, Heidelberg, Germany, 2 Deutsches Krebsforschungszentrum, DKFZ-ZMBH Allianz, Heidelberg, Germany Abstract Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early- branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a ‘‘double-cut’’ elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several c