ArticleProceedings of the National Academy of Sciences of the United States of America2009
Distinct and overlapping roles for two Dicer-like proteins in the RNA interference pathways of the ancient eukaryote Trypanosoma brucei.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 63 citations in OpenAlex.
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- Tetracycline-Inducible Functional Complementation Analysis in Trypanosoma Parasites.Methods in molecular biology (Clifton, N.J.) · 2026Article
- MANY PATHS TO DESTRUCTION: FAMILY-SPECIFIC TURNOVER AND STRESS RESPONSES FOR TRNA INTRONS.bioRxiv : the preprint server for biology · 2025Article
- Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes.Nature communications · 2024Article
- Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Current Status of Regulatory Non-Coding RNAs Research in the Tritryp.Non-coding RNA · 2022Review
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- In Response to Abiotic Stress, DNA Methylation Confers EpiGenetic Changes in Plants.Plants (Basel, Switzerland) · 2021Review
- Reliable, scalable functional genetics in bloodstream-form Trypanosoma congolense in vitro and in vivo.PLoS pathogens · 2021Article
- AtxA-Controlled Small RNAs ofFrontiers in microbiology · 2020Article
- Increased Affinity for RNA Targets Evolved Early in Animal and Plant Dicer Lineages through Different Structural Mechanisms.Molecular biology and evolution · 2017Article
- The Evolutionary Loss of RNAi Key Determinants in Kinetoplastids as a Multiple Sporadic Phenomenon.Journal of molecular evolution · 2017Article
- RNA damage in biological conflicts and the diversity of responding RNA repair systems.Nucleic acids research · 2016Review
- A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei.Nucleic acids research · 2016Article
- Honey bee microRNAs respond to infection by the microsporidian parasite Nosema ceranae.Scientific reports · 2015Article
- NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway.Nucleic acids research · 2015Article
- Article
- The evolutionary journey of Argonaute proteins.Nature structural & molecular biology · 2014Review
- Genome of the avirulent human-infective trypanosome--Trypanosoma rangeli.PLoS neglected tropical diseases · 2014Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
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Abstract
Trypanosoma brucei is one of the most ancient eukaryotes where RNA interference (RNAi) is operational and is the only single-cell pathogen where RNAi has been extensively studied and used as a tool for functional analyses. Here, we report that the T. brucei RNAi pathway, although relying on a single Argonaute protein (AGO1), is initiated by the activities of two distinct Dicer-like enzymes. Both TbDCL1, a mostly cytoplasmic protein, and the previously undescribed nuclear enzyme TbDCL2 contribute to the biogenesis of siRNAs from retroposons. However, TbDCL2 has a predominant role in generating siRNAs from chromosomal internal repeat transcripts that accumulate at the nucleolus in RNAi-deficient cells and in initiating the endogenous RNAi response against retroposons and repeats alike. Moreover, siRNAs generated by both TbDCL1 and TbDCL2 carry a 5'-monophosphate and a blocked 3' terminus, suggesting that 3' end modification is an ancient trait of siRNAs. We thus propose a model whereby TbDCL2 fuels the T. brucei nuclear RNAi pathway and TbDCL1 patrols the cytoplasm, posttranscriptionally silencing potentially harmful nucleic acid parasites that may access the cytoplasm. Nevertheless, we also provide evidence for cross-talk between the two Dicer-like enzymes, because TbDCL2 is implicated in the generation of 35- to 65-nucleotide intermediate transcripts that appear to be substrates for TbDCL1. Our finding that dcl2KO cells are more sensitive to RNAi triggers than wild-type cells has significant implications for reverse genetic analyses in this important human pathogen.
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