Transcriptional and Post-Transcriptional Control of Tubulin Gene Expression in<i>Trypanosoma cruzi</i>

Tp, Urményi; Ft, De Castro; Jf, Carvalho; W, de Souza; Rondinelli, Edson

doi:10.1089/dna.1992.11.101

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…However, in L. mexicana , similar amounts of tubulin mRNAs were found in both promastigotes and amastigotes [28,29]. In the related trypanosomatid T. cruzi , the regulation of tubulin genes has been studied in some extent [30,31]. In this parasite, lower levels of the α- and β-tubulin transcripts are found in amastigotes and trypomastigotes compared to epimastigotes.…”

Section: Resultsmentioning

confidence: 99%

Alpha tubulin genes from Leishmania braziliensis:genomic organization, gene structure and insights on their expression

2013

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BackgroundAlpha tubulin is a fundamental component of the cytoskeleton which is responsible for cell shape and is involved in cell division, ciliary and flagellar motility and intracellular transport. Alpha tubulin gene expression varies according to the morphological changes suffered by Leishmania in its life cycle. However, the objective of studying the mechanisms responsible for the differential expression has resulted to be a difficult task due to the complex genome organization of tubulin genes and to the non-conventional mechanisms of gene regulation operating in Leishmania.ResultsWe started this work by analyzing the genomic organization of α-tubulin genes in the Leishmania braziliensis genome database. The genomic organization of L. braziliensis α-tubulin genes differs from that existing in the L. major and L. infantum genomes. Two loci containing α-tubulin genes were found in the chromosomes 13 and 29, even though the existence of sequence gaps does not allow knowing the exact number of genes at each locus. Southern blot assays showed that α-tubulin locus at chromosome 13 contains at least 8 gene copies, which are tandemly organized with a 2.08-kb repetition unit; the locus at chromosome 29 seems to contain a sole α-tubulin gene. In addition, it was found that L. braziliensis α-tubulin locus at chromosome 13 contains two types of α-tubulin genes differing in their 3′ UTR, each one presumably containing different regulatory motifs. It was also determined that the mRNA expression levels of these genes are controlled by post-transcriptional mechanisms tightly linked to the growth temperature. Moreover, the decrease in the α-tubulin mRNA abundance observed when promastigotes were cultured at 35°C was accompanied by parasite morphology alterations, similar to that occurring during the promastigote to amastigote differentiation.ConclusionsInformation found in the genome databases indicates that α-tubulin genes have been reorganized in a drastic manner along Leishmania speciation. In the L. braziliensis genome database, two loci containing α-tubulin sequences were found, but only the locus at chromosome 13 contains the prototypic α-tubulin genes, which are repeated in a head-to-tail manner. Also, we determined that the levels of α-tubulin mRNAs are down-regulated drastically in response to heat shock by a post-transcriptional mechanism which is dependent upon active protein synthesis.

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Section: Resultsmentioning

confidence: 99%

Alpha tubulin genes from Leishmania braziliensis:genomic organization, gene structure and insights on their expression

2013

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“…There is a large family of tubulin proteins but the α/β heterodimer is the essential building material for the microtubular cytoskeleton [ 9 ]. Trypanosomatid parasites possess an extensive array of cytoplasmic, mitotic and flagellar microtubules and recent evidence suggests that tubulin expression varies greatly during the life cycles of Trypanosoma and Leishmania spp., possibly as the relative demand for these structures fluctuates [ 10 - 14 ]. Indeed, in certain species, different isoforms of tubulin may have specific expression profiles related to the parasitic life cycle; for example, L. mexicana has a β-tubulin isoform unique to the amastigote stage found within human macrophages [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution of Tubulin Gene Arrays in Trypanosomatid parasites: genomic restructuring in Leishmania

2006

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Background: α-and β-tubulin are fundamental components of the eukaryotic cytoskeleton and cell division machinery. While overall tubulin expression is carefully controlled, most eukaryotes express multiple tubulin genes in specific regulatory or developmental contexts. The genomes of the human parasites Trypanosoma brucei and Leishmania major reveal that these unicellular kinetoplastids possess arrays of tandem-duplicated tubulin genes, but with differences in organisation. While L. major possesses monotypic α and β arrays in trans, an array of alternating α-and β tubulin genes occurs in T. brucei. Polycistronic transcription in these organisms makes the chromosomal arrangement of tubulin genes important with respect to gene expression.

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“…Higher levels of unpolymerised tubulins were found in amastigotes and trypomastigotes, which suggests that there is an autoregulatory mechanism to induce tubulin mRNA destabilisation in these two stages of the parasite life cycle (da Silva et al 2006). Furthermore, treatment of epimastigotes with vinblastine, a drug that prevents microtubule assembly, reduced alpha and beta tubulin mRNAs levels, whereas the levels of GAPDH mRNA were unchanged (Urményi et al 1992 In an attempt to identify regulatory elements involved in modulating the half-lives of alpha and beta tubulin transcripts in response to changes in microtubule dynamics, epimastigotes were transiently transfected with vectors containing the luciferase gene associated with different regions of these mRNAs. These analyses clearly indicated the presence of elements in the 3' UTR of alpha tubulin transcripts that are responsible for the increased stability of this mRNA in epimastigotes (Araújo et al 2011).…”

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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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Transcriptional and Post-Transcriptional Control of Tubulin Gene Expression inTrypanosoma cruzi

Cited by 12 publications

References 37 publications

Alpha tubulin genes from Leishmania braziliensis:genomic organization, gene structure and insights on their expression

Alpha tubulin genes from Leishmania braziliensis:genomic organization, gene structure and insights on their expression

Evolution of Tubulin Gene Arrays in Trypanosomatid parasites: genomic restructuring in Leishmania

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

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