Regulatory elements involved in the post-transcriptional control of stage-specific gene expression in Trypanosoma cruzi: a review

Abstract

Trypanosoma cruzi is an intracellular parasite that is transmitted by at least 40 different blood-sucking triatomine species to over 1,000 mammalian species (Brener et al. 2000). This parasite must adapt to enormous changes in its extracellular milieu, such as changes in environmental temperature as well as in the available nutrients inside each host. The parasite has a complex life cycle that is characterised by four stages; epimastigotes and metacyclic trypomastigotes are present in the insect vector, whereas intracellular amastigotes and bloodstream trypomastigotes are present in the mammalian host. Thus, this species must develop a broad set of molecular tools that allow it to multiply in the insect gut, to invade and multiply inside a large number of distinct mammalian cell types and to circumvent host immune defence systems. To meet such phenotypic plasticity, T. cruzi relies on unique mechanisms that can control the expression of its repertoire of about 12,000 genes. Because its genome is constitutively transcribed into long polycistronic primary transcripts, mRNAs for proteincoding genes must be processed through trans-splicing and polyadenylation reactions. The mRNAs must also interact with different protein factors in a complex posttranscriptional regulatory machinery that determines the levels of their protein product according to the cellular demands of the parasite in each stage of its life cycle.In the same issue that the T. cruzi genome was published (El-Sayed et al. 2005a), a study describing its proteome was also reported (Atwood et al. 2005). Proteins extracted from whole-cell and subcellular lysates of the four stages of T. cruzi were analysed by mass spectrometry (epimastigotes, metacyclic trypomastigotes, amastigotes and trypomastigotes), which identified 2,784 proteins belonging to the 1,168 protein groups in the annotated T. cruzi genome. Although about 30% of the identified proteins were found at all life-cycle stages, at least 248 proteins were only expressed at one stage, thereby demonstrating significant changes in the relative abundance of T. cruzi proteins throughout its life cycle. One of the main findings in these proteomic analyses was that the four parasite stages use distinct energy sources (Atwood et al. 2005); intracellular amastigotes upregulated proteins involved in lipid-dependent energy metabolism, such as enzymes of the citric acid cycle, whereas enzymes capable of catalysing the conversion of histidine to glutamate were more abundant in the insect epimastigote stage. Heat-shock proteins (HSP) and proteins involved in vesicular trafficking were also preferentially detected in amastigotes. Furthermore, enzymes involved in antioxidant defence were upregulated during the transformation of epimastigotes into invasive metacyclic trypomastigotes, whereas bloodstream trypomastigotes upregulated the surface expression of several large gene families that are known to be involved in interacting with the mammalian host (Atwood et al. 2005).In agreement with this proteomics data, glo...

TcTASV-C, a Protein Family in Trypanosoma cruzi that Is Predominantly Trypomastigote-Stage Specific and Secreted to the Medium

“…This is particularly interesting since it opens an additional question about the regulation mechanism of expression of surface proteins in T. cruzi . Protein translation in trypanosomatids is tightly regulated by the interaction of cis-acting elements (mainly the 3′ UTR of the genes) and RNA binding proteins [57]. In the case of the TcTASV-C family, the 3′UTR is highly conserved, and is actually a ‘hallmark” of the gene family.…”

The MASP Family of Trypanosoma cruzi: Changes in Gene Expression and Antigenic Profile during the Acute Phase of Experimental Infection

“…We did not detect a correlation between chromosomal location of the MASP genes sampled in our cDNA libraries and their expression levels (data not shown), suggesting that there is no apparent bias regarding the chromosomal location of expressed MASP genes. It is well established that the control of gene expression in Trypanosomatids operates almost exclusively at a post-transcription level, primarily mediated by regulatory elements with the 3′UTR of the transcripts that modulate the mRNA stability by means of interactions with regulatory proteins [reviewed in 54]. We have previously shown that the 3′UTR of MASP transcripts is highly conserved among the family members [5] and therefore may not be involved in the differential expression of the distinct MASP genes.…”

Genome-wide analysis of 3′-untranslated regions supports the existence of post-transcriptional regulons controlling gene expression in trypanosomes

“…Several studies demonstrated the presence of U-rich elements in trypanosomal mRNA 3′-UTRs [reviewed in Araujo & Teixeira, 2011; Haile & Papadopoulou, 2007; Hendriks & Matthews, 2007]. Strikingly, the functional role of CA repeated tracts in T. cruzi 3′-UTRs was recently established as a signal for gene expression modulation through the parasite’s life-cycle (Pastro et al, 2013).…”