ArticlePLoS pathogens2012
Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and provides insight into the core machinery.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Computational discovery of conserved RNA structures and functional characterization of a structured lncRNA inNon-coding RNA research · 2025Article
- 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
- Strain-specific genome evolution in Trypanosoma cruzi, the agent of Chagas disease.PLoS pathogens · 2021Article
- RNA damage in biological conflicts and the diversity of responding RNA repair systems.Nucleic acids research · 2016Review
- Structure-based approach to the identification of a novel group of selective glucosamine analogue inhibitors of Trypanosoma cruzi glucokinase.Molecular and biochemical parasitology · 2015Article
- Identification of AGO3-associated miRNAs and computational prediction of their targets in the green alga Chlamydomonas reinhardtii.Genetics · 2015Article
- Genome of the avirulent human-infective trypanosome--Trypanosoma rangeli.PLoS neglected tropical diseases · 2014Article
- The evolutionary journey of Argonaute proteins.Nature structural & molecular biology · 2014Review
- Trypanosoma cruzi-secreted vesicles have acid and alkaline phosphatase activities capable of increasing parasite adhesion and infection.Parasitology research · 2014Article
- The CAF1-NOT complex of trypanosomes.Frontiers in genetics · 2014Review
- Role of the Trypanosoma brucei HEN1 family methyltransferase in small interfering RNA modification.Eukaryotic cell · 2014Article
- An automated graphics tool for comparative genomics: the Coulson plot generator.BMC bioinformatics · 2013Article
- The structure and repertoire of small interfering RNAs in Leishmania (Viannia) braziliensis reveal diversification in the trypanosomatid RNAi pathway.Molecular microbiology · 2013Article
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- Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei.BMC genomics · 2012Article
- New perspectives on the diversification of the RNA interference system: insights from comparative genomics and small RNA sequencing.Wiley interdisciplinary reviews. RNAReview
- Trypanosome RNA editing: the complexity of getting U in and taking U out.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3'-5' exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites.
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