ArticlePLoS pathogens2010
Persistent ER stress induces the spliced leader RNA silencing pathway (SLS), leading to programmed cell death in Trypanosoma brucei.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 87 citations in OpenAlex.
- Thermo-related degeneration of stumpy forms of Trypanosoma brucei, the pathogen of African sleeping sickness.Advanced biotechnology · 2025Article
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- Core-Shell DNA-Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes.Chembiochem : a European journal of chemical biology · 2022Article
- Graphene quantum dots induce cascadic apoptosisFrontiers in immunology · 2022Article
- The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy.Frontiers in cellular and infection microbiology · 2022Review
- Article
- Antiparasitic Effect of Stilbene and Terphenyl Compounds againstPharmaceuticals (Basel, Switzerland) · 2021Article
- Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis.Frontiers in microbiology · 2021Review
- Developmentally Regulated Novel Non-coding Anti-sense Regulators of mRNA Translation iniScience · 2020Article
- Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase.PLoS neglected tropical diseases · 2020Article
- Porcine reproductive and respiratory syndrome virus infection induces endoplasmic reticulum stress, facilitates virus replication, and contributes to autophagy and apoptosis.Scientific reports · 2020Article
- GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress inFrontiers in cellular and infection microbiology · 2020Article
- An essential thioredoxin-type protein of Trypanosoma brucei acts as redox-regulated mitochondrial chaperone.PLoS pathogens · 2019Article
- Stress susceptibility in Trypanosoma brucei lacking the RNA-binding protein ZC3H30.PLoS neglected tropical diseases · 2018Article
- Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.Traffic (Copenhagen, Denmark) · 2018Article
- Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei.PLoS neglected tropical diseases · 2018Article
- Identification of di-substituted ureas that prevent growth of trypanosomes through inhibition of translation initiation.Scientific reports · 2018Article
- Participation of dengue virus NS4B protein in the modulation of immune effectors dependent on ER stress in insect cells.Cell stress & chaperones · 2017Article
- Exosome secretion affects social motility in Trypanosoma brucei.PLoS pathogens · 2017Article
- Antiparasitic lethality of sulfonamidebenzamides in kinetoplastids.Bioorganic & medicinal chemistry letters · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Trypanosomes are parasites that cycle between the insect host (procyclic form) and mammalian host (bloodstream form). These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR). However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS) pathway. SLS elicits shut-off of spliced leader RNA (SL RNA) transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER) stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD), evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS) production, increase in cytoplasmic Ca(2+), and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM). ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.
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