Abstract
Trypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programmed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and have their expression controlled by post-transcriptional mechanisms. Transcriptome analyses comparing three stages of the T. cruzi life cycle revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBPs), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP, named TcZH3H12, which contains a zinc finger domain and is up-regulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout (KO) epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Transcriptome analyses comparing wild type and TcZC3H12 KOs revealed a TcZC3H12-dependent expression of epimastigote-specific genes such as genes encoding amino acid transporters and proteins associated with differentiation (PADs). RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.
Highlights
Trypanosoma cruzi, the causative agent of Chagas disease, affects approximately 6–8 million people worldwide
Members of the beta amastin sub-family, whose epimastigote-specific expressions have been previously described by our group (Kangussu-Marcolino et al, 2013), as well as members of the family of PADs, which have been characterized in T. brucei (Dean et al, 2009) but not in T. cruzi, were found among the genes that are up-regulated in CL Brener epimastigotes (Table S5)
Trypanosoma cruzi is a member of an early divergent group of eukaryotic organisms that is characterized by unique features with respect to genome organization and gene expression
Summary
Trypanosoma cruzi, the causative agent of Chagas disease, affects approximately 6–8 million people worldwide. It is endemic in Latin America, where it is a major public health problem and causes over 10 000 deaths annually (WHO, 2020). When taking a blood meal on an infected mammal, the insect vector ingests circulating trypomastigotes, which, once inside the insect midgut, differentiate into replicative epimastigotes. In the posterior end of the digestive tract, epimastigotes differentiate into infective, non-dividing metacyclic trypomastigotes, which are eliminated with the insect’s urine and feces during a blood meal. Trypomastigotes cause lysis of the infected cells, reach the circulatory system and propagate the infection by entering new cells or being ingested by a vector (Brener, 1973)
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