Characterization of a Trypanosoma cruzi poly(A)-binding protein and its genes

Batista, João A. N.; Teixeira, Santuza Maria Ribeiro; Donelson, John E.; Kirchhoff, Louis V.; Sá, Cezar Martins de

doi:10.1016/0166-6851(94)00133-2

Cited by 41 publications

(33 citation statements)

References 33 publications

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“…Similar observations were obtained for other transcripts of regulatory proteins (e.g. TcPABP1 among others) (25). 3 We conclude that, with the exception of Tcrbp6, Tcrbp mRNA steady-state levels are quite similar between different developmental stages of the parasite.…”

Section: Tcrbps a Family Of Rrm-containing Rna-binding Proteins In Tsupporting

confidence: 81%

RNA Recognition Motif-type RNA-binding Proteins in Trypanosoma cruzi Form a Family Involved in the Interaction with Specific Transcripts in Vivo

Gaudenzi¹,

D’Orso²,

Frasch

2003

Journal of Biological Chemistry

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Trypanosomes, protozoan parasites from the order Kinetoplastida, have to deal with environmental changes during the interaction with their hosts. Trypanosoma cruzi, the causative agent of Chagas' disease, uses post-transcriptional mechanisms to regulate gene expression. However, few RNA-binding proteins involved in mRNA turnover control have been identified to date. In this work, an RNA recognition motif (RRM)-type RNA-binding protein family named T. cruzi RNAbinding protein (TcRBP) and composed of at least six members was identified. The genomic organization of four members revealed a head to tail arrangement within a region of 15 kilobase pairs. TcRBP members have a common RRM and different auxiliary domains with a high content of glycine, glutamine, and histidine residues within their N-and C-terminal regions. TcRBPs differ in their expression patterns as well as in their homoribopolymer binding interaction in vitro, although they preferentially recognize poly(U) and poly(G) RNAs. An interesting observation was the relaxed RNA-binding interactions with several trypanosome transcripts in vitro. In contrast, co-immunoprecipitation experiments of TcRBP-containing ribonucleoprotein complexes formed in vivo revealed a highly restricted binding interaction with specific RNAs. Several TcRBPcontaining complexes are stage-specific and, in some cases, bear the poly(A)-binding protein TcPABP1. Altogether, these results suggest that TcRBPs might be modulated in vivo, to favor or preclude the interaction with specific transcripts in a developmentally regulated manner.Trypanosoma cruzi, the etiological agent of Chagas' disease, is a unicellular digenetic protozoan parasite with a complex life cycle that alternates between an insect and a vertebrate host, with different replicative and infective stages in both organisms. The parasite has a wide range of mammalian hosts, from humans to wild and domestic animal species, that act as reservoirs (1). T. cruzi infection is established in the mammal by the insect-derived stage metacyclic trypomastigote that differentiates to the intracellular replicative amastigote stage. This parasite form differentiates to the infective trypomastigote in the mammal, which is released from cells and circulates in blood, infecting other cells and being eventually ingested by the insect with its blood meal. Ingested trypomastigotes differentiate to epimastigotes (the replicative insect stage) that migrate along the digestive tract until differentiation into metacyclic trypomastigotes that are eliminated with the feces closing the cycle. Because the parasite suffers continuous environmental changes, it needs to regulate the expression of many proteins to allow its rapid adaptation. In contrast to other eukaryotic organisms, trypanosomatids do not regulate gene expression at the classical level of transcription initiation (2), although an RNA polymerase II transcriptional complex was recently identified (3). Transcription in these organisms is polycistronic, and the main point of regulation of gene e...

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Section: Tcrbps a Family Of Rrm-containing Rna-binding Proteins In Tsupporting

confidence: 81%

RNA Recognition Motif-type RNA-binding Proteins in Trypanosoma cruzi Form a Family Involved in the Interaction with Specific Transcripts in Vivo

Gaudenzi¹,

D’Orso²,

Frasch

2003

Journal of Biological Chemistry

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“…During stress, alterations in these protein complexes could mediate mRNA storage or degradation to reduce translational rates . Among the limited number of RBPs involved in the T. cruzi mRNA metabolism that have been characterized are poly(A)-binding protein (Batista et al 1994), TcUPB1 (D'Orso & Frasch 2001, SLRBP (Xu et al 2001), Pumilio proteins (PUF) (Dallagiovanna et al 2005, Caro et al 2006, zinc finger proteins (Espinosa et al 2003, Mörking et al 2004) and the RNAhelicase TcDHH1 (Holetz et al 2007).…”

Section: Rna-binding Proteins Are Essential Trans-acting Elements Formentioning

confidence: 99%

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

Araújo

Teixeira

2011

Mem. Inst. Oswaldo Cruz

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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...

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“…Following this principle the sequence targeted in this work which is 159 residues long and is predicted to weight 18 kDa, showed to be homologous to poly-A binding proteins from trypanosomatids and other eukaryotes (Table). The first Trypanosomatidae PABP1 to have its gene cloned and sequenced was from T. cruzi (Batista et al 1994). This protein (TcPABP1) has 66 kDa and is similar to PABP1 of other eukaryotic organisms, which show molecular weights ranging from 64-73 kDa.…”

Section: Discussionmentioning

confidence: 99%

“…However, we propose that LaPABP sequence can correspond to a full functional protein. Our hypothesis is supported by a number of evidences: (i) it is estimated that LmPAB1 would account for only 50% of the cytoplasmic poly(A) binding activity observed in L. major cultures, suggesting the presence of another abundant RNA binding protein which would interact with poly(A) tails with lower affinity (Bates et al 2000); (ii) it has been shown that only two RRM are necessary for RNA binding in vitro and that the first two RRMs in PABP bind polyadenylate with higher affinity than the third and fourth domains do (Nietfeld et al 1990); (iii) the PABP from the lower eukaryotes Dictyostelium discoideum and Physarum polycephalum were reported to have lower molecular weights than exhibited by the PABP from more complex organisms (hence with a different architecture from the classical PABP) but still showing a significant poly-A binding activity (Batista et al 1994). However, the lack of a number of residues (less than 20) corresponding to the remainder of the second RRM domain could indicate that the clone obtained really correspond to a Cterminal truncated form of this parsimonious version of the observed PABP domain architecture.…”

Section: Discussionmentioning

confidence: 99%

“…However, the lack of a number of residues (less than 20) corresponding to the remainder of the second RRM domain could indicate that the clone obtained really correspond to a Cterminal truncated form of this parsimonious version of the observed PABP domain architecture. Nevertheless, two observations encouraged us to consider that the sequence analyzed could still correspond to a functional protein in vivo: (i) the second RBD found in the PABP1 from T. cruzi is also incomplete (Batista et al 1994); (ii) although being incomplete, the second RBD from LaPABP presents both motifs involved in the recognition of RNA (RNP1 and RNP2; data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Molecular Modeling Approaches for Determining Gene Function: application to a Putative Poly-A Binding Protein from Leishmania amazonensis (LaPABP)

Silva-Jr

Veyl²,

Clos³

et al. 2002

Mem. Inst. Oswaldo Cruz

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Characterization of a Trypanosoma cruzi poly(A)-binding protein and its genes

Cited by 41 publications

References 33 publications

RNA Recognition Motif-type RNA-binding Proteins in Trypanosoma cruzi Form a Family Involved in the Interaction with Specific Transcripts in Vivo

RNA Recognition Motif-type RNA-binding Proteins in Trypanosoma cruzi Form a Family Involved in the Interaction with Specific Transcripts in Vivo

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

Molecular Modeling Approaches for Determining Gene Function: application to a Putative Poly-A Binding Protein from Leishmania amazonensis (LaPABP)

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