Trypanosoma cruzi XRNA granules colocalise with distinct mRNP granules at the nuclear periphery

Costa, Jimena Ferreira da; Ferrarini, Mariana Galvão; Nardelli, Sheila Cristina; Goldenberg, Samuel; Ávila, Andréa Rodrigues; Holetz, Fabíola

doi:10.1590/0074-02760170531

Cited by 7 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TcSgn1 localization was, in fact, altered in the presence of sinefungin, resulting in its distribution at the periphery of the nucleus and weak staining in the cytoplasm. A similar alteration was also shown for the exonuclease XRNA and RNA helicase DHH1 [ 36 ]. With sinefungin, both proteins colocalized at the nuclear periphery.…”

Section: Discussionsupporting

confidence: 74%

Characterization of the RNA-Binding Protein TcSgn1 in Trypanosoma cruzi

et al. 2021

Self Cite

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) participate in several steps of post-transcriptional regulation of gene expression, such as splicing, messenger RNA transport, mRNA localization, and translation. Gene-expression regulation in trypanosomatids occurs primarily at the post-transcriptional level, and RBPs play important roles in the process. Here, we characterized the RBP TcSgn1, which contains one RNA recognition motif (RRM). TcSgn1 is a close ortholog of yeast Saccharomyces cerevisiae protein ScSgn1, which plays a role in translational regulation in the cytoplasm. We found that TcSgn1 in Trypanosoma cruzi is localized in the nucleus in exponentially growing epimastigotes. By performing immunoprecipitation assays of TcSgn1, we identified hundreds of mRNAs associated with the protein, a significant fraction of them coding for nucleic acids binding, transcription, and endocytosis proteins. In addition, we show that TcSgn1 is capable of interacting directly with the poly(A) tail of the mRNAs. The study of parasites under nutritional stress showed that TcSgn1 was localized in cytoplasmic granules in addition to localizing in the nucleus. Similar to ScSgn1, we observed that TcSgn1 also interacts with the PABP1 protein, suggesting that this protein may play a role in regulating gene expression in T. cruzi. Taken together, our results show that RNA-binding protein TcSgn1 is part of ribonucleoprotein complexes associated with nuclear functions, stress response, and RNA metabolism.

show abstract

Section: Discussionsupporting

confidence: 74%

Characterization of the RNA-Binding Protein TcSgn1 in Trypanosoma cruzi

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The RNP granules described in T. cruzi [ 104 , 105 ] contain similar components to yeast or mammalian processing bodies (P-bodies), e.g., TcDHH1, and TcXRNA proteins. These proteins are expressed through the parasite life cycle and are localized in cytoplasmic foci that vary in number according to nutritional stress conditions and cycloheximide/puromycin treatment [ 106 , 107 ]. TcDHH1 and TcXRNA co-localize only at the nuclear periphery under cellular stress conditions and when the mRNA processing is inhibited [ 107 ].…”

Section: The Importance Of Rnp Granules In Modulating Gene Expression...mentioning

confidence: 99%

Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

“…This differentiation is called metacyclogenesis and can be induced in vitro : epimastigotes, usually cultured in carbon-rich medium (liver infusion tryptose, LIT), are concentrated and transferred to an acidic medium lacking carbon sources (triatomine artificial urine medium, TAU) and subsequently to TAU supplemented with three amino acids (TAU3AAG, proline, glutamate, aspartate) for four days [38] (Figure 1A). Experiments that aim to investigate molecular mechanisms involved in T. cruzi differentiation focus mainly on two stages of this process: (i) starvation in TAU medium for two hours, which induces global translation arrest, polysome disassembly, eIF2α phosphorylation [39], [40] and formation of stress granules [41], [42], [43], and (ii) recovery in TAU3AAG, which causes a partial return in translation [40].…”

Section: Introductionmentioning

confidence: 99%

Two distinctTrypanosomaeIF4F complexes co-exist, bind different mRNAs and are regulated during nutritional stress

Gabiatti,

Freire,

da Costa

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Many eIF4F subunits and PABP paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types or developmental stages. Each eIF4F complex has its own proteins, mRNAs and, consequently, a distinct function. We set out to study the function and regulation of the two major eIF4F complexes of Trypanosoma cruzi. We identified the associated proteins and mRNAs of eIF4E3 and eIF4E4 in cells in exponential growth and in nutritional stress. Upon stress, eIF4G/eIF4A and PABP remain associated to the eIF4E, but the association with other 43S pre-initiation factors decreases, indicating that ribosome attachment is impaired. Most eIF4E3-associated mRNAs encode for metabolic proteins, while eIF4E4 associate to mRNAs encoding ribosomal proteins. Interestingly, for both eIF4E3/4, more mRNAs were associated in stressed cells than in non-stressed cells, even though these mRNAs have lower translational efficiencies in stress. In summary, trypanosomes have two co-existing eIF4F complexes involved in translation of distinct mRNA cohorts important for growth. Under stress conditions, both complexes exit translation but remain bound to their mRNA targets.

show abstract

Trypanosoma cruzi XRNA granules colocalise with distinct mRNP granules at the nuclear periphery

Cited by 7 publications

References 30 publications

Characterization of the RNA-Binding Protein TcSgn1 in Trypanosoma cruzi

Characterization of the RNA-Binding Protein TcSgn1 in Trypanosoma cruzi

Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

Two distinctTrypanosomaeIF4F complexes co-exist, bind different mRNAs and are regulated during nutritional stress

Contact Info

Product

Resources

About