Extensive Translational Regulation through the Proliferative Transition of Trypanosoma cruzi Revealed by Multi-Omics

Chávez, Santiago Solís; Urbaniak, Michael D.; Benz, Corinna; Smircich, Pablo; Garat, Beatríz; Sotelo‐Silveira, José; Duhagon, Marı́a Ana

doi:10.1128/msphere.00366-21

Cited by 13 publications

(7 citation statements)

References 82 publications

(131 reference statements)

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“…The DGCs are transcribed as large polycistronic transcription units (PTUs) (Johnson et al, 1987), and messenger RNA maturation implies co-transcriptional trans-splicing of spliced leader RNA and polyadenylation (Matthews et al, 1994). Consequently, post-transcriptional regulation has been proposed as the main gene expression regulation level (Clayton et al 2007 and 2019; Chávez et al, 2021). However, it is not sufficient to explain the critical regulatory changes necessary for pathogenicity, and recent reports have highlighted the relevance of histone posttranslational modifications, histone variants, base J, and chromatin organization on the regulation of gene expression, cell cycle control, differentiation and pathogenesis (Maree et al, 2022;Faria et al, 2021;Respuela et al, 2008;Rosón et al, 2022;Nunes et al, 2020;Ramos et al,2015).…”

Section: Mainmentioning

confidence: 99%

3D genome organization drives gene expression in trypanosomes

Díaz-Viraqué

Chiribao

Libisch

et al. 2023

Preprint

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In trypanosomes, eukaryotic unicellular pathogens that cause disabling human and animal diseases, very few transcriptional regulatory elements have been described and it is largely accepted that they regulate gene expression mainly post-transcriptionally. In this regard, the role of the spatial organization of the genome on gene expression and vice versa remains practically unexplored. The genome of these parasites is partitioned into core (highly conserved syntenic) and species-specific disruptive regions (synteny disruption), containing multigene families encoding for surface glycoproteins. By mapping genome-wide chromatin interactions we demonstrate that these regions constitute 3D compartments (C and D). These chromatin compartments present significant differences in DNA methylation, nucleosome positioning and chromatin interactions, affecting genome expression dynamics. We show that the genome is organized into chromatin folding domains and transcription is dramatically determined by the local chromatin structure. Our results support a model in which epigenetic mechanisms dramatically impact gene expression in these eukaryotic pathogens.

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Section: Mainmentioning

confidence: 99%

3D genome organization drives gene expression in trypanosomes

Díaz-Viraqué

Chiribao

Libisch

et al. 2023

Preprint

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“…However, trypanosomatids have developed strategies that differentiate them from other eukaryotes. The mechanisms related to the gene regulation in T. cruzi include alterations in gene expression, mainly at the post-transcriptional level, since its genes are transcribed as long polycistronic units produced by RNA polymerase II and then processed into single and mature transcripts [ 67 , 68 ].…”

Section: Gene Expression Regulation Of Significant Virulence Factorsmentioning

confidence: 99%

Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

et al. 2022

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Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. This protozoan developed several mechanisms to infect, propagate, and survive in different hosts. The specific expression of proteins is responsible for morphological and metabolic changes in different parasite stages along the parasite life cycle. The virulence strategies at the cellular and molecular levels consist of molecules responsible for mediating resistance mechanisms to oxidative damage, cellular invasion, and immune evasion, performed mainly by surface proteins. Since parasite surface coat remodeling is crucial to invasion and infectivity, surface proteins are essential virulence elements. Understanding the factors involved in these processes improves the knowledge of parasite pathogenesis. Genome sequencing has opened the door to high-throughput technologies, allowing us to obtain a deeper understanding of gene reprogramming along the parasite life cycle and identify critical molecules for survival. This review therefore focuses on proteins regulated during differentiation into infective forms considered virulence factors and addresses the current known mechanisms acting in the modulation of gene expression, emphasizing mRNA signals, regulatory factors, and protein complexes.

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“…Despite having been discovered more than 30 years ago [ 6 ], the role of DGF-1 remains a mystery. Here, we summarize the most relevant findings concerning this gene family, provide some clues about its potential function, and discuss the incongruences between the DGF-1 transcriptome and proteome results [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Elusive Trypanosoma cruzi Disperse Gene Protein Family (DGF-1)

Ramı́rez

2023

Pathogens

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Chagas disease, caused by Trypanosoma cruzi infections, is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the T. cruzi genome, the number of molecular and biochemical studies on this parasite has increased considerably, many of which are focused on families of variant surface proteins, especially trans-sialidases, mucins, and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the T. cruzi genome; however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. However, here we argue that given the ubiquitous presence in all T. cruzi species, and physicochemical characteristics, the DGF-1 gene family may play and important role in host-parasite interactions.

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Extensive Translational Regulation through the Proliferative Transition of Trypanosoma cruzi Revealed by Multi-Omics

Cited by 13 publications

References 82 publications

3D genome organization drives gene expression in trypanosomes

3D genome organization drives gene expression in trypanosomes

Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

The Elusive Trypanosoma cruzi Disperse Gene Protein Family (DGF-1)

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