Cell Biology of the Trypanosome Genome

Abstract

SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

The Major Protein Arginine Methyltransferase in Trypanosoma brucei Functions as an Enzyme-Prozyme Complex

“…In the search for new treatments, understanding the basic biology of the parasite is a cornerstone on the path to discovery of novel biological processes that could potentially serve as drug targets (2). Despite the eukaryotic nature of T. brucei, the organism has been shown to harbor many unique biological processes or, in some cases, to extensively utilize mechanisms that are rarely used in higher eukaryotes (3)(4)(5). The exceptional biology of trypanosomes is likely a consequence of their long separate evolutionary history and numerous adaptations to the parasitic lifestyle (6).…”

“…Strikingly, these organisms accomplish adaptations to changing environments and differentiation to several distinct life cycle forms all in the absence of transcriptional control of their genome (3). Rather, gene expression is regulated at posttranscriptional and posttranslational levels.…”

The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation

“…The transcription of protein-coding genes in Kinetoplastid protists by RNA polymerase II is polycistronic (Palenchar and Bellofatto 2006;Daniels et al 2010). Individual mRNAs are excised by 5 ′ trans splicing of a "spliced leader" (SL) and 3 ′ polyadenylation (Michaeli 2011).…”

Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development

“…The kinetoplastid genome is arranged in gene clusters, and transcription produces polycistronic transcripts. Regulation of gene expression appears to be primarily posttranscriptional, via modulation of the splicing machinery that generates the mature mRNAs (67). Moreover, their histone sequences and the PTMs that decorate them deviate from what is observed in other eukaryotes (68)(69)(70)(71)(72).…”