Trypanosoma cruzi: Analysis of the complete PUF RNA-binding protein family

Caro, Florence; Bercovich, Natalia; Atorrasagasti, Catalina; Levìn, Mariano J.; Vázquez, Martı́n

doi:10.1016/j.exppara.2005.12.015

Cited by 32 publications

(36 citation statements)

References 25 publications

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“…There are 10 T. brucei PUF proteins whose structures resemble those of the T. cruzi PUFs [10]. We did however note the presence of a predicted transmembrane helix in TbPUF3 and a putative mitochondrial localization signal in TbPUF5.…”

Section: The 10 Puf Proteins Of T Bruceimentioning

confidence: 64%

“…The kinetoplastid genome sequences predict the presence of 10 PUF protein family members [10]. More primitive organisms, including C. elegans and S. cerevisiae, possess multiple PUF proteins, whereas only one PUF protein (with two isoforms) is present in Drosophila.…”

Section: Introductionmentioning

confidence: 99%

“…T. cruzi PUF6 [12] and PUF1 [10], and the two Puf proteins of P. falciparum, PfPuf1 and PfPuf2 [13], were shown to bind specifically to the Drosophila hunchback Puf recognition sequence in vitro but no further functional information on these proteins is available. T. cruzi PUF3, 5 and 8 did not show binding to the sequence in a three-hybrid assay [10].…”

Section: Introductionmentioning

confidence: 99%

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Functional analysis of Trypanosoma brucei PUF1

Luu

Brems

Hoheisel

et al. 2006

Molecular and Biochemical Parasitology

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The genomes of Trypanosoma brucei, Leishmania major and Trypanosoma cruzi each encode 10 proteins with PUF domains. PUF domain proteins from yeast and metazoa have been shown to bind RNA and to regulate mRNA stability and translation. Phylogenetic analysis suggested that the PUF proteins were duplicated and diverged early in evolution, and that most PUF proteins were lost during the evolution of mammals. Depletion of any of the first nine T. brucei PUF protein mRNAs by RNA interference had no effect on cell growth; combined depletion of PUF1 and PUF3, PUF3 and PUF4, and PUF1 and PUF4 mRNAs also had no effect. In conflict with a previous report, procyclic trypanosomes lacking PUF1 genes grew normally and we could find no evidence that PUF1 is required for growth of trypanosomes in culture. Depletion or elimination of PUF1 mRNA did not affect the abundances of any other mRNAs, as detected in microarray analysis, and also had minimal effects on the proteome. (In control experiments, treatment of bloodstream and procyclic cells with 100 ng/ml tetracycline also had no detectable effects on the transcriptome and proteome.) PUF1 preferentially bound to retroposon RNAs and was not associated with polysomes. We suggest that, as in yeast, there may be functional redundancy among the Kinetoplastid PUF proteins, or they may be involved in fine-tuning gene expression together with other proteins. Alternatively, PUF proteins may be needed in differentiating trypanosomes or in non-culturable life-cycle stages.

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Section: The 10 Puf Proteins Of T Bruceimentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional analysis of Trypanosoma brucei PUF1

Luu

Brems

Hoheisel

et al. 2006

Molecular and Biochemical Parasitology

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“…An example was reported during the characterization of members from the Puf (Pumilio) family, which have been extensively studied in trypanosomatids [49][50][51][52]. TcPUF6 over-expression in T. cruzi and a microarray approach allowed a comparative analysis of RNA from transfected and control parasites; this study showed that TcPUF6 had a significant effect on overall gene expression.…”

Section: Tczfp1mentioning

confidence: 99%

“…The targets include genes for mitochondrial proteins and protein kinases. [50] TcUBP1 RRM Involved in mRNA destabilization in vivo through binding to AU-rich elements at the 3'-UTR of SMUG mucin mRNAs. Part of complex containing TcPUF2 and TcPABP1.…”

Section: Rbp Complexes and Gene Expression Regu-lationmentioning

confidence: 99%

Functional Genomics and Insights into Trypanosoma cruzi Gene Expression Regulation

Ávila

Goldenberg

2010

TOPARAJ

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Abstract:The regulation of gene expression in trypanosomatids is predominantly post-transcriptional. Polycistronic transcripts are processed by the addition of a common 5'-spliced leader and polyadenylation. However, the processed mRNAs are not necessarily functionally related, suggesting the existence of mechanisms for the degradation or storage of untranslatable mRNAs. Determination of the TriTryps (Leishmania major, Trypanosoma brucei and Trypanosoma cruzi) genome sequences has allowed the identification of genes encoding potential regulatory proteins. This review discusses some of the mechanisms and regulatory elements involved in cytoplasmic gene expression regulation in Trypanosoma cruzi. We also discuss how functional genomic tools have contributed toward determining the role played by RNA binding protein complexes, supporting the concept of "post-transcriptional RNA operons" or "RNA regulons". This suggests the existence of interconnected regulatory networks in the parasite, in which RNA granules act as protagonists in cytoplasmic mRNA metabolism.Keywords: Trypanosoma cruzi, RNA binding protein, gene expression regulation, functional genomics. TRANSCRIPTION OF MESSENGER RNATrypanosoma cruzi (T. cruzi) is the protozoan parasite causing Chagas disease, a major disease endemic to Latin America. It belongs to the Kinetoplastida order and has a complex life cycle, alternating between insect vectors and mammalian hosts. In both hosts, T. cruzi goes through morphological and functional changes, creating non-infective and infective forms. Those changes resulted from selective adaptation and are the major consequence of differential gene expression. Being a single cell, it needs to quickly regulate the synthesis of several proteins for rapid adaptation to a different environment. Its protein synthesis has particular characteristics in comparison with higher eukaryotes. For example, the protein-coding genes are organized into polycistronic transcription units; however, in contrast to what occurs in bacterial operons, the polycistronic units must be transcriptionally processed together before translation. In this case, polycistronic RNAs are converted into monocistronic messenger RNAs (mRNAs) through two coupled events: trans-splicing and polyadenylation. During transsplicing, a 39-nt spliced leader (SL) RNA molecule is joined to the 5' terminus of the mature transcript, while a poly(A) tail is polymerized at the 3' terminus. The same polycistronic RNA can contain functionally unrelated genes, which yield very different steady-state mRNA levels and/or which are differentially expressed during the life cycle [see review inAnother trypanosome transcription characteristic is the absence of defined RNA polymerase II (pol II) promoters. There are a few exceptions, however, such as the genes *Address correspondence to these authors at the Instituto Carlos Chagas -ICC, Fiocruz-Paraná, Rua Prof. Algacyr Munhoz Madder 3775, Curitiba, PR. Brazil; Tel: +55-41-33163230; Fax: +55-41-33163267; E-mails: sgoldenb@fiocruz.br, aravi...

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Transcriptome and Functional Genomics Reveal the Participation of Adenine Phosphoribosyltransferase in Trypanosoma cruzi Resistance to Benznidazole

García-Huertas

Mejía-Jaramillo

González

et al. 2017

J of Cellular Biochemistry

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Currently, the only available treatments for Trypanosoma cruzi are benznidazole (Bz) and nifurtimox (Nfx). The mechanisms of action and resistance to these drugs in this parasite are not complete known. In order to identify differentially expressed transcripts between sensitive and resistant parasites, a massive pyrosequencing of the T. cruzi transcriptome was carried out. Additionally, the 2D gel electrophoresis profile of sensitive and resistant parasites was analyzed and the data were supported with functional genomics. The results showed 133 differentially expressed genes in resistant parasites. The transcriptome analysis revealed the regulation of different genes with several functions and metabolic pathways, which could suggest that resistance in T. cruzi is a multigenic process. Additionally, using transcriptomics, one gene, adenine phosphoribosyltransferase (APRT), was found to be down-regulated in the resistant parasites and its expression profile was confirmed by 2D electrophoresis analysis. The role of this gene in the resistance to Bz was confirmed overexpressing it in sensitive and resistant parasites. Interestingly, both parasites became more sensitive to Bz and H O . This is the first RNA-seq study to identify regulated genes in T. cruzi associated with Bz resistance and to show the role of APRT in T. cruzi resistance. Although T. cruzi regulation is mainly post-transcriptional, the transcriptome analysis, supported by 2D gel analysis and functional genomic, provides an overall idea of the expression profiles of genes under resistance conditions. These results contribute essential information to further the understanding of the mechanisms of action and resistance to Bz in T. cruzi. J. Cell. Biochem. 118: 1936-1945, 2017. © 2017 Wiley Periodicals, Inc.

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Trypanosoma cruzi: Analysis of the complete PUF RNA-binding protein family

Cited by 32 publications

References 25 publications

Functional analysis of Trypanosoma brucei PUF1

Functional analysis of Trypanosoma brucei PUF1

Functional Genomics and Insights into Trypanosoma cruzi Gene Expression Regulation

Transcriptome and Functional Genomics Reveal the Participation of Adenine Phosphoribosyltransferase in Trypanosoma cruzi Resistance to Benznidazole

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