Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei

Nilsson, Daniel; Gunasekera, Kapila; Mani, Jan; Østerås, Magne; Farinelli, Laurent; Baerlocher, Loïc; Roditi, Isabel; Ochsenreiter, Torsten

doi:10.1371/journal.ppat.1001037

Cited by 170 publications

(230 citation statements)

References 61 publications

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“…Although the expression levels of TbSAS-4 in the two developmental forms are not known, TbSAS-4 mRNA is among the most highly down-regulated transcripts during the differentiation to epimastigote cells by ablation of ALBA3/4 (45), RNA-binding proteins that are also involved in cell morphology transitions (27). Similarly, ClpGM6 mRNA was also down-regulated by depletion of ALBA3/4 (15,45). These results suggest that life cycle form transitions in T. brucei may be regulated at the posttranscriptional level by RNA-binding protein-mediated modulation of the expression of certain FAZ-associated cytoskeletal proteins, such as ClpGM6 and TbSAS-4.…”

Section: Discussionmentioning

confidence: 99%

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

Zhou

2015

Journal of Biological Chemistry

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The centrosome in animals constitutes the cell's microtubule-organizing center that nucleates spindle assembly, and is characterized by a symmetrical array of nine microtubule triplets emanating from a cartwheel structure in the very proximal region of the centriole. Biogenesis of centrioles requires many regulatory proteins, including SAS-6, SAS-4/CPAP, and BLD10/CEP135, which are thought to constitute the core ancestral module involved in centriole assembly (1). The three proteins have distinct functions in centriole biogenesis. SAS-6 assembles to the cartwheel (2, 3) and BLD10/CEP135 forms the pinhead that connects the cartwheel spokes to the A-microtubules of the microtubule triplets (4, 5), whereas SAS-4/CPAP controls the elongation of centriolar microtubules (6 -9).Trypanosoma brucei, a flagellated protozoan and the causative agent of human sleeping sickness, does not have centrosomes, but it possesses the basal body as its microtubule-organizing center to nucleate the assembly of a motile flagellum. The basal body is characterized by an array of nine microtubule triplets, with the conserved SAS-6 protein forming the cartwheel structure (10), similar to that of the centrosome in metazoa. The flagellum is attached, along most of its length, to the cell body via a specialized cytoskeletal structure termed the flagellum attachment zone (FAZ), 2 which consists of three main domains: the structure connecting the paraflagellar rod (PFR) to the flagellar membrane, the structure connecting the flagellar membrane and the cell body membrane, and a cytoplasmic filament (often referred to as the FAZ filament) and its associated microtubule quartet (11)(12)(13)(14)(15)(16)(17). In addition to mediating flagellum-cell body attachment, the FAZ filament also defines the cytokinesis cleavage plane (11,12), with the distal tip of the new FAZ filament marking the site of cytokinesis initiation (18 -20). Moreover, during the cell cycle in the procyclic form, the elongation of the FAZ filament positions the newly assembled basal body toward the cell posterior (21), which is crucial for organelle segregation and cell division (10,(22)(23)(24)(25).Trypanosomatids, a group of kinetoplastid parasites consisting of T. brucei, Trypanosoma cruzi, and Leishmania spp., appear in a variety of different morphological forms during their life cycle and are distinguished by the relative position of the kinetoplast (mitochondrial DNA) and the nucleus and by the position, length, and cell body attachment of the flagellum (26). In the tsetse fly vector, T. brucei differentiates from the trypomastigote form to the epimastigote form, which undergoes asymmetrical cell division to produce a long epimastigote cell and a short epimastigote cell (26). How life cycle transitions in T. brucei are regulated is largely unknown, but recent work has begun to uncover the regulators involved in this process. ALBA3 and ALBA4, two closed related RNA-binding proteins, are the first factors found to be involved in life cycle transitions in T. brucei (27). Anothe...

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Section: Discussionmentioning

confidence: 99%

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

Zhou

2015

Journal of Biological Chemistry

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“…Even though the transcriptome of bloodstream and insect procyclic-forms is ~30% distinct 15 , we tested whether insect procyclic trypanosomes share a circadian transcriptome temperature-entraining with 23°C/28°C cycles ( Fig. 1a and Supplementary Fig.…”

Section: Bloodstream and Insect Procyclic-form Parasites Have An Intrmentioning

confidence: 99%

Trypanosoma brucei metabolism is under circadian control

et al. 2017

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TX 75390-9111, USAThe Earth's rotation forced life to evolve under cyclic day and night environmental changes. In order to anticipate such daily cycles, prokaryote and eukaryote free-living organisms evolved intrinsic clocks that regulate physiological and behavioral processes. Daily rhythms have been observed in organisms living within hosts, such as parasites. Whether parasites have intrinsic molecular clocks or whether they simply respond to host rhythmic physiological cues remains unknown. Here we show that Trypanosoma brucei, the causative agent of human sleeping sickness, has an intrinsic circadian clock that regulates its metabolism in two different stages of the life cycle. We found that in vitro approximately 10% of genes in T. brucei are expressed with a circadian rhythm. The maximum expression of these genes occurs at two different phases of the day and may depend on a posttranscriptional mechanism. Circadian genes are enriched in cellular metabolic pathways, and coincide with two peaks of intracellular ATP concentration. Moreover, daily changes in the parasite population lead to differences in suramin sensitivity, a drug commonly used to treat Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature

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“…Using an updated gene model based on spliced leader trapping studies (Nilsson et al 2010;Siegel et al 2010), in silico-translated MRB8620 contains a predicted hydrophobic stretch of amino acids toward the N-terminus that may serve as a transmembrane domain (Fig. 1A), as determined using the TMHMM 2.0 program (Möller et al 2001).…”

Section: Mrb8620 Associates With the Inner Mitochondrial Membranementioning

confidence: 99%

Integrity of the core mitochondrial RNA-binding complex 1 is vital for trypanosome RNA editing

Huang

Faktorová

Křížová

et al. 2015

RNA

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Trypanosoma brucei is the causative agent of the human and veterinarian diseases African sleeping sickness and nagana. A majority of its mitochondrial-encoded transcripts undergo RNA editing, an essential process of post-transcriptional uridine insertion and deletion to produce translatable mRNA. Besides the well-characterized RNA editing core complex, the mitochondrial RNA-binding 1 (MRB1) complex is one of the key players. It comprises a core complex of about six proteins, guide RNA-associated proteins (GAPs) 1/2, which form a heterotetramer that binds and stabilizes gRNAs, plus MRB5390, MRB3010, and MRB11870, which play roles in initial stages of RNA editing, presumably guided by the first gRNA:mRNA duplex in the case of the latter two proteins. To better understand all functions of the MRB1 complex, we performed a functional analysis of the MRB8620 core subunit, the only one not characterized so far. Here we show that MRB8620 plays a role in RNA editing in both procyclic and bloodstream stages of T. brucei, which reside in the tsetse fly vector and mammalian circulatory system, respectively. While RNAi silencing of MRB8620 does not affect procyclic T. brucei fitness when grown in glucose-containing media, it is somewhat compromised in cells grown in the absence of this carbon source. MRB8620 is crucial for integrity of the MRB1 core, such as its association with GAP1/2, which presumably acts to deliver gRNAs to this complex. In contrast, GAP1/2 is not required for the fabrication of the MRB1 core. Disruption of the MRB1 core assembly is followed by the accumulation of mRNAs associated with GAP1/2.

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Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei

Cited by 170 publications

References 61 publications

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament

Trypanosoma brucei metabolism is under circadian control

Integrity of the core mitochondrial RNA-binding complex 1 is vital for trypanosome RNA editing

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