TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Trypanosoma Brucei
SUBMITTER: 
Tamar Ziv
LAB HEAD: Shulamit Michaeli
PROVIDER: PXD049995 | Pride | 2025-04-06
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 80197-200_71388-9.rar | Other | |||
| 81017-9txt.rar | Other | |||
| 88495-500_txt.zip | Other | |||
| Seq71388_HF.raw | Raw | |||
| Seq71389_HF.raw | Raw |
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Project description:Trypanosoma brucei subspecies infect humans and animals in sub-Saharan Africa. This early diverging eukaryote shows many novel features in basic biological processes, including the use of polycistronic transcription to generate all protein-coding mRNAs. Therefore we hypothesized that translational control provides a means to tune gene expression during parasite development in mammalian and fly hosts. We used ribosome profiling to examine genome-wide protein production in animal-derived slender bloodstream forms and cultured procyclic (insect midgut) forms. About one-third of all CDSs showed statistically significant regulation of protein production between the two stages. Of these, more than two-thirds showed a change in translation efficiency, but few were controlled by this parameter alone. Ribosomal proteins were translated poorly, especially in animal-derived parasites. A disproportionate number of metabolic enzymes were up-regulated at the mRNA level in procyclic forms, as were variant surface glycoproteins in bloodstream forms. Comparison with cultured bloodstream forms from another strain identified stage-specific changes in protein production that transcend strain and growth conditions. Genes with upstream ORFs had a lower mean translation efficiency but no evidence was seen for involvement of these ORFs in stage-regulation. Ribosome profiling revealed that differences in the production of specific proteins in T. brucei slender bloodstream and procyclic forms are more common than anticipated from analysis of mRNA abundance. While in vivo and in vitro derived slender bloodstream forms of different strains are more similar to one another than to procyclic forms, they showed numerous differences at both the mRNA and protein production level.
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Project description:Trypanosoma brucei subspecies infect humans and animals in sub-Saharan Africa. This early diverging eukaryote shows many novel features in basic biological processes, including the use of polycistronic transcription to generate all protein-coding mRNAs. Therefore we hypothesized that translational control provides a means to tune gene expression during parasite development in mammalian and fly hosts. We used ribosome profiling to examine genome-wide protein production in animal-derived slender bloodstream forms and cultured procyclic (insect midgut) forms. About one-third of all CDSs showed statistically significant regulation of protein production between the two stages. Of these, more than two-thirds showed a change in translation efficiency, but few were controlled by this parameter alone. Ribosomal proteins were translated poorly, especially in animal-derived parasites. A disproportionate number of metabolic enzymes were up-regulated at the mRNA level in procyclic forms, as were variant surface glycoproteins in bloodstream forms. Comparison with cultured bloodstream forms from another strain identified stage-specific changes in protein production that transcend strain and growth conditions. Genes with upstream ORFs had a lower mean translation efficiency but no evidence was seen for involvement of these ORFs in stage-regulation. Ribosome profiling revealed that differences in the production of specific proteins in T. brucei slender bloodstream and procyclic forms are more common than anticipated from analysis of mRNA abundance. While in vivo and in vitro derived slender bloodstream forms of different strains are more similar to one another than to procyclic forms, they showed numerous differences at both the mRNA and protein production level. Ribosome profiling and mRNA libraries were constructed in triplicate from in vitro PCF and in vivo BF lifestages of theT. brucei Treu927 and in vitro T. brucei Lister427, to evaluate role of translational gene regulation
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Project description:Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. In this study, we refined the previously published mathematical model for bloodstream form parasites and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Through this study, we conclude that lLevels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting acquisition of new control mechanisms during adaptation to mammalian parasitism. Ribosome profiling and mRNA libraries were constructed in triplicate from in vitro PCF and in duplicate from in vitro T. brucei Lister427, to understand global differntial gene transcription.
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Project description:Trypanosoma brucei occupies distinct niches throughout its life cycle, both within the vertebrate host (fat tissue, bloodstream, central nervous system) and within the insect host, the tsetse fly (taken up with a bloodmeal and passing through the midgut, and migrating to the salivary glands). The immunological and biochemical complexity and variability of each of these environments require a reshaping of the protein landscape of the parasite both to evade surveillance and face changing metabolic demands. Whereas most well-studied organisms rely on transcriptional control as the main regulator of gene expression, post-transcriptional control mechanisms are particularly important in T. brucei, and these are often mediated by RNA-binding proteins. DRBD18 is a T. brucei RNA binding protein that interacts with ribosomal proteins and translation factors. Here, we tested a role for DRBD18 in translational control. We show that DRBD18 depletion by RNA interference leads to altered polysomal profiles with a specific depletion of heavy polysomes. RiboSeq analysis reveals that 101 transcripts change in translational efficiency (TE) upon DRBD18 depletion: 41 of them exhibit decreased TE and 60 increased TE. A further 66 transcripts are buffered, i.e. changes in transcript abundance are compensated by changes in TE such that the total translational output is expected not to change. Proteomic analysis validates much of these data. In DRBD18 depleted cells, a cohort of transcripts that code for procyclic form specific proteins are translationally repressed while, conversely, transcripts that code for bloodstream form specific proteins are translationally enhanced. These data suggest that DRBD18 contributes to the maintenance of the procyclic state through both positive and negative translational control of specific mRNAs.
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Project description:The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically M-bM-^@M-^Xslender formsM-bM-^@M-^Y to transmissible M-bM-^@M-^Xstumpy formsM-bM-^@M-^Y through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched in throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms), irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been identified to enrich transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream haves been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms. Examination of gene expression during life cycle stages.
2013-12-16 | E-GEOD-46388 | biostudies-arrayexpress
Project description:The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically ‘slender forms’ to transmissible ‘stumpy forms’ through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched in throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms), irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been identified to enrich transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream haves been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms.
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