Conversion of procyclic-form Trypanosoma brucei to the bloodstream form by transient expression of RBP10

Mugo, Elisha; Egler, Franziska; Clayton, Christine

doi:10.1016/j.molbiopara.2017.06.009

Cited by 14 publications

(13 citation statements)

References 16 publications

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“…In a separate manuscript, we have recently shown that after induction RBP10 expression in procyclic forms, and culture for two days in procyclic conditions, the cells are not infective for mice. However, after transient transfection of an RBP10 expression plasmid, growth for two days in procyclic medium, and culture for 3 weeks in bloodstream-form culture conditions, the resulting trypanosomes were indeed infective and showed stumpy form development at peak parasitaemia [ 78 ]. These results indicate that the presence of RBP10 primes procyclic forms for growth as bloodstream forms, but the temperature and medium shift is required to complete the differentiation process.…”

Section: Resultsmentioning

confidence: 99%

Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei

2017

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In nearly all eukaryotes, cellular differentiation is governed by changes in transcription, and stabilized by chromatin and DNA modification. Gene expression control in the pathogen Trypanosoma brucei, in contrast, relies almost exclusively on post-transcriptional mechanisms, so RNA binding proteins must assume the burden that is usually borne by transcription factors. T. brucei multiply in the blood of mammals as bloodstream forms, and in the midgut of Tsetse flies as procyclic forms. We show here that a single RNA-binding protein, RBP10, promotes the bloodstream-form trypanosome differentiation state. Depletion of RBP10 from bloodstream-form trypanosomes gives cells that can grow only as procyclic forms; conversely, expression of RBP10 in procyclic forms converts them to bloodstream forms. RBP10 binds to procyclic-specific mRNAs containing an UAUUUUUU motif, targeting them for translation repression and destruction. Products of RBP10 target mRNAs include not only the major procyclic surface protein and enzymes of energy metabolism, but also protein kinases and stage-specific RNA-binding proteins: this suggests that alterations in RBP10 trigger a regulatory cascade.

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Section: Resultsmentioning

confidence: 99%

Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei

2017

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“…This difference suggests that glucose availability may influence activation of metabolic pathways required for different developmental stages. To assess if the gene expression pattern was uniquely associated with glucose depletion, the transcriptome changes in response to glucose depletion were compared to transcriptional data generated from analysis of nine other transcriptomes ( Table S4 ) ( 17 , 25 , 29 , 31 – 36 ). The analyses include transcriptomes from pleomorphic EATRO1125 LS and PF and pleomorphic TREU927 LS and PF generated from mouse-derived SS parasites with 6 mM cis -aconitate, monomorphic Lister 427 BF and lab-adapted PF parasites, and monomorphic BF (Lister 427) parasites with RBP10 knocked down.…”

Section: Discussionmentioning

confidence: 99%

“…S4 ). The cells used in the five treatments were maintained in media that contained at least 5 mM glucose ( 17 , 23 , 31 , 33 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

Glucose Signaling Is Important for Nutrient Adaptation during Differentiation of Pleomorphic African Trypanosomes

Qiu

Milanes

Jones

et al. 2018

mSphere

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As the African trypanosome Trypanosoma brucei completes its life cycle, it encounters many different environments. Adaptation to these environments includes modulation of metabolic pathways to parallel the availability of nutrients. Here, we describe how the blood-dwelling life cycle stages of the African trypanosome, which consume glucose to meet their nutritional needs, respond differently to culture in the near absence of glucose. The proliferative long slender parasites rapidly die, while the nondividing short stumpy parasite remains viable and undergoes differentiation to the next life cycle stage, the procyclic form parasite. Interestingly, a sugar analog that cannot be used as an energy source inhibited the process. Furthermore, the growth of procyclic form parasite that resulted from the event was inhibited by glucose, a behavior that is similar to that of parasites isolated from tsetse flies. Our findings suggest that glucose sensing serves as an important modulator of nutrient adaptation in the parasite.

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“…This organism replicates in the blood and tissue fluids of mammals (as bloodstream forms) and in the digestive system of tsetse flies (often as procyclic forms). During their migration towards the salivary glands, the procyclic forms differentiate into mesocyclic or epimastigote forms, and in the salivary glands, epimastigotes transform into non-replicative metacyclic forms that can infect mammals 3 . During their transition in different environments and due to their frequent replication, DNA lesions often form that can lead to genomic instability.…”

Section: Introductionmentioning

confidence: 99%

Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment

Marin

Silva

Pavani

et al. 2018

Sci Rep

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One of the most important mechanisms for repairing double-strand breaks (DSBs) in model eukaryotes is homologous recombination (HR). Although the genes involved in HR have been found in Trypanosoma brucei and studies have identified some of the proteins that participate in this HR pathway, the recruitment kinetics of the HR machinery onto DNA during DSB repair have not been clearly elucidated in this organism. Using immunofluorescence, protein DNA-bound assays, and DNA content analysis, we established the recruitment kinetics of the HR pathway in response to the DSBs generated by ionizing radiation (IR) in procyclic forms of T. brucei. These kinetics involved the phosphorylation of histone H2A and the sequential recruitment of the essential HR players Exo1, RPA, and Rad51. The process of DSB repair took approximately 5.5 hours. We found that DSBs led to a decline in the G2/M phase after IR treatment, concomitant with cell cycle arrest in the G1/S phase. This finding suggests that HR repairs DSBs faster than the other possible DSB repair processes that act during the G1/S transition. Taken together, these data suggest that the interplay between DNA damage detection and HR machinery recruitment is finely coordinated, allowing these parasites to repair DNA rapidly after DSBs during the late S/G2 proficient phases.

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Conversion of procyclic-form Trypanosoma brucei to the bloodstream form by transient expression of RBP10

Cited by 14 publications

References 16 publications

Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei

Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei

Glucose Signaling Is Important for Nutrient Adaptation during Differentiation of Pleomorphic African Trypanosomes

Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment

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