2025
TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei
Galili-Kostin B, Rajan K, Ida Ashkenazi Y, Freedman A, Doniger T, Cohen-Chalamish S, Waldman Ben-Asher H, Unger R, Roditi I, Tschudi C, Michaeli S. TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei. Nature Communications 2025, 16: 3697. PMID: 40251171, PMCID: PMC12008373, DOI: 10.1038/s41467-025-58979-w.Peer-Reviewed Original ResearchConceptsProcyclic formsNon-coding RNAsLong non-coding RNAsPolycistronic transcription unitsRNA polymerase I.RNA polymerase IProtozoan parasite Trypanosoma bruceiRegulate gene expressionParasite Trypanosoma bruceiTsetse fly vectorComplex life cycleInsect midgutProcyclin genesSocial motilityLate procyclic formsRegulating developmental changesTranscription unitPolymerase I.Polymerase IBase pairsMammalian hostsTrypanosoma bruceiChanging abundanceInsect hostsTarget mRNAsDeep mutational scanning of the Trypanosoma brucei developmental regulator RBP6 reveals an essential disordered region influenced by positive residues
Rojas-Sánchez S, Kolev N, Tschudi C. Deep mutational scanning of the Trypanosoma brucei developmental regulator RBP6 reveals an essential disordered region influenced by positive residues. Nature Communications 2025, 16: 1168. PMID: 39885181, PMCID: PMC11782513, DOI: 10.1038/s41467-025-56553-y.Peer-Reviewed Original ResearchConceptsN-terminal intrinsically disordered regionRNA binding protein 6RNA recognition motifDeep mutational scanningMutational scanningDisordered regionsProtein-RNA interactionsIntrinsically disordered regionsComplex developmental programPositively charged residuesSingle-point variantsProtein-RNARNA recognitionDeleterious mutationsMutational constraintsProcyclic formsAnimal African trypanosomiasisTrypanosoma bruceiCharged residuesPrimary structureRegained infectivityDevelopmental programRegulatory roleProtein 6Positive residues
2024
Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei
Beaver A, Keneskhanova Z, Cosentino R, Weiss B, Awuoche E, Smallenberger G, Buenconsejo G, Crilly N, Smith J, Hakim J, Zhang B, Bobb B, Rijo-Ferreira F, Figueiredo L, Aksoy S, Siegel T, Mugnier M. Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei. Nature 2024, 636: 430-437. PMID: 39478231, PMCID: PMC11634766, DOI: 10.1038/s41586-024-08151-z.Peer-Reviewed Original ResearchVariant surface glycoproteinAntigenic diversityAntigenic variationHigh-throughput sequencing approachDense variant surface glycoproteinPopulations of T. bruceiDynamics of antigenic variationGenomic repertoirePathogen diversificationSequencing approachExtravascular spaceTrypanosoma bruceiVariation in vivoHost immune systemAntigenic variation in vivoSurface glycoproteinSlow immune responseDiversitySwitching expressionParasite populationsAurora B controls anaphase onset and error-free chromosome segregation in trypanosomes
Ballmer D, Lou H, Ishii M, Turk B, Akiyoshi B. Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes. Journal Of Cell Biology 2024, 223: e202401169. PMID: 39196069, PMCID: PMC11354203, DOI: 10.1083/jcb.202401169.Peer-Reviewed Original ResearchConceptsAurora BAnaphase onsetMetaphase-to-anaphase transitionPromote mitotic exitComplex regulatory circuitryEarly-branching eukaryotesKinetochore-microtubule attachmentsAurora B activityDelays anaphase onsetAurora B kinaseCell cycle progressionSpindle assembly checkpointKinetochore proteinsMitotic exitOuter kinetochoreChromosome segregationChromosome missegregationRegulatory circuitrySpindle microtubulesAurora B inhibitionCycle progressionTrypanosoma bruceiAssembly checkpointB kinaseKinetochore
2023
Two cold shock domain containing proteins trigger the development of infectious Trypanosoma brucei
Toh J, Nkouawa A, Dong G, Kolev N, Tschudi C. Two cold shock domain containing proteins trigger the development of infectious Trypanosoma brucei. PLOS Pathogens 2023, 19: e1011438. PMID: 37276216, PMCID: PMC10270622, DOI: 10.1371/journal.ppat.1011438.Peer-Reviewed Original ResearchConceptsCold shock domainMetacyclic parasitesRegulation of transcriptionMicrotubule-based movementProtozoan parasite Trypanosoma bruceiCold shock proteinsRNA-binding proteinC-terminal domainFamily of DNAN-terminal domainDNA damage repairParasite Trypanosoma bruceiSpecific binding motifAmino acid residuesMammalian infectivityNucleocytoplasmic transportDevelopmental programProcyclic parasitesTrypanosoma bruceiCSD2CSD1MRNA stabilityBiological functionsBinding motifBiological processes
2022
Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei
Rajan KS, Adler K, Doniger T, Cohen-Chalamish S, Aharon-Hefetz N, Aryal S, Pilpel Y, Tschudi C, Unger R, Michaeli S. Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei. Journal Of Biological Chemistry 2022, 298: 102141. PMID: 35714765, PMCID: PMC9283944, DOI: 10.1016/j.jbc.2022.102141.Peer-Reviewed Original ResearchConceptsRNA modificationsLife stagesStage-specific regulationGenome-wide approachesSmall nucleolar RNAsΨ modificationsSmall noncoding RNAsDifferent host environmentsProtein translocationD snoRNAsRRNA modificationVault RNARRNA processingNucleolar RNAsRiboMeth-seqNoncoding RNAsMammalian hostsTrypanosoma bruceiProtein synthesisHost environmentRNAFunctional implicationsTRNABruceiParasites
2021
Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei
Toh JY, Nkouawa A, Sánchez SR, Shi H, Kolev NG, Tschudi C. Identification of positive and negative regulators in the stepwise developmental progression towards infectivity in Trypanosoma brucei. Scientific Reports 2021, 11: 5755. PMID: 33707699, PMCID: PMC7952579, DOI: 10.1038/s41598-021-85225-2.Peer-Reviewed Original ResearchConceptsGene expression regulatory networksMetacyclic variant surface glycoproteinSingle RNA-binding proteinExpression regulatory networksRNA-binding proteinTsetse fly vectorBloodstream form trypanosomesAlanine-rich proteinPutative nucleic acidRNA-seq dataSubset of transcriptsCell linesDevelopmental progressionVariant surface glycoproteinMitochondrial genomeOverexpression cell linesFunction phenotypesRegulatory networksProcyclic trypanosomesTrypanosoma bruceiNegative regulatorRich proteinImportant humanMetacyclic parasitesGenes
2020
Single-cell RNA sequencing of Trypanosoma brucei from tsetse salivary glands unveils metacyclogenesis and identifies potential transmission blocking antigens
Vigneron A, O'Neill MB, Weiss BL, Savage AF, Campbell OC, Kamhawi S, Valenzuela JG, Aksoy S. Single-cell RNA sequencing of Trypanosoma brucei from tsetse salivary glands unveils metacyclogenesis and identifies potential transmission blocking antigens. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 2613-2621. PMID: 31964820, PMCID: PMC7007551, DOI: 10.1073/pnas.1914423117.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingInfectious metacyclic formsMetacyclic parasitesMammalian host environmentFly salivary glandsMajor cell clustersClustering of cellsTsetse salivary glandsFamily proteinsDevelopmental programMammalian hostsMetacyclic cellsProtein transcriptsTrypanosoma bruceiDevelopmental processesGene expressionAfrican trypanosomesExpression profilesMolecular mechanismsSalivary glandsNew hostSurface localizationTrypanosome transmissionMetacyclogenesis
2019
The vault RNA of Trypanosoma brucei plays a role in the production of trans-spliced mRNA
Kolev NG, Rajan KS, Tycowski KT, Toh JY, Shi H, Lei Y, Michaeli S, Tschudi C. The vault RNA of Trypanosoma brucei plays a role in the production of trans-spliced mRNA. Journal Of Biological Chemistry 2019, 294: 15559-15574. PMID: 31439669, PMCID: PMC6816085, DOI: 10.1074/jbc.ra119.008580.Peer-Reviewed Original ResearchConceptsTelomerase-associated protein 1Vault RNAY RNAsRNA quality controlRNA polymerase IIISmall nuclear RNATrans-spliced mRNAPermeabilized cell systemNcRNA repertoireRNP biogenesisMRNA metabolismRNA speciesSequence similarityRNA classesMammalian cellsNuclear RNAPolymerase IIIRo functionTrypanosoma bruceiVtRNAsGene expressionRo proteinBloodstream formsRNACell nuclei
2017
The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion
Christiano R, Kolev NG, Shi H, Ullu E, Walther TC, Tschudi C. The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion. Molecular Microbiology 2017, 106: 74-92. PMID: 28742275, PMCID: PMC5607103, DOI: 10.1111/mmi.13754.Peer-Reviewed Original ResearchConceptsInfectious metacyclic formsTsetse fly vectorMetacyclic formsVariant surface glycoprotein expression sitesQuiescent cellsGene expression profilesFly vectorsAvailability of nutrientsMammalian invasionsCell surface componentsCell divisionProcyclic trypanosomesMammalian hostsTrypanosoma bruceiMRNA sequencingExpression profilesExpression sitesMetabolic enzymesBloodstream formsInfectious metacyclicsProtein 6TranscriptomeTsetse fliesProteomeProtein levelsThe Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei
Chikne V, Gupta SK, Doniger T, K. SR, Cohen-Chalamish S, Ben-Asher HW, Kolet L, Yahia NH, Unger R, Ullu E, Kolev NG, Tschudi C, Michaeli S. The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei. Journal Of Molecular Biology 2017, 429: 3301-3318. PMID: 28456523, DOI: 10.1016/j.jmb.2017.04.015.Peer-Reviewed Original ResearchConceptsNon-coding RNAsPoly (ADP-ribose) polymeraseUnique RNA processing mechanismsCis-spliced intronsRNA processing mechanismsSmall nucleolar RNAsLong non-coding RNAsPolyadenylation of mRNAParasite Trypanosoma bruceiSnoRNA biogenesisTrans splicingPrecursor snoRNASnoRNA processingNucleolar RNAsPAP1Trypanosoma bruceiPolyadenylationMajor substrateSnoRNAsTrypanosoma cruziPAP2RNAPolymerase Pap1TrypanosomesCausative agent
2015
Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich repertoire of RNAs involved in modification and processing of rRNA
Eliaz D, Doniger T, Tkacz ID, Biswas VK, Gupta SK, Kolev NG, Unger R, Ullu E, Tschudi C, Michaeli S. Genome-wide analysis of small nucleolar RNAs of Leishmania major reveals a rich repertoire of RNAs involved in modification and processing of rRNA. RNA Biology 2015, 12: 1222-1255. PMID: 25970223, PMCID: PMC4829279, DOI: 10.1080/15476286.2015.1038019.Peer-Reviewed Original ResearchConceptsSmall nucleolar RNAsNucleolar RNAsGenome-wide analysisRNA processing mechanismsRRNA secondary structurePost-transcriptional levelCore proteinProcessing of rRNARNA-seq analysisFunctional homologueGene clusterRNA speciesTrypanosoma bruceiSnoRNAsComplete repertoireGene expressionRRNA cleavageAnalogous functionsSecondary structureRNAProtozoan parasiteRich repertoireOrganismsSpeciesProtein
2014
Construction of Trypanosoma brucei Illumina RNA-Seq Libraries Enriched for Transcript Ends
Kolev NG, Ullu E, Tschudi C. Construction of Trypanosoma brucei Illumina RNA-Seq Libraries Enriched for Transcript Ends. Methods In Molecular Biology 2014, 1201: 165-175. PMID: 25388113, DOI: 10.1007/978-1-4939-1438-8_9.Peer-Reviewed Original ResearchConceptsHuman pathogen Trypanosoma bruceiHigh-throughput RNA sequencingLong polycistronic precursorsGenome-wide scaleIllumina RNA-seqPathogen Trypanosoma bruceiRNA polymerase IIRNA-seq librariesSingle-nucleotide resolutionTranscript endsTranscript boundariesTranscriptome annotationUnannotated genesPolymerase IICellular abundancePolycistronic precursorsTranscription initiationGene clusterRNA-seqPolyadenylation sitesRNA sequencingMRNA precursorsTrypanosoma bruceiRNA moleculesMRNA moleculesThe emerging role of RNA‐binding proteins in the life cycle of Trypanosoma brucei
Kolev NG, Ullu E, Tschudi C. The emerging role of RNA‐binding proteins in the life cycle of Trypanosoma brucei. Cellular Microbiology 2014, 16: 482-489. PMID: 24438230, PMCID: PMC3974610, DOI: 10.1111/cmi.12268.Peer-Reviewed Original ResearchConceptsParasitic protozoan Trypanosoma bruceiIdentification of RBPsTargets of RBPsSpecific gene networksProtozoan Trypanosoma bruceiPost-transcriptional mechanismsGene regulatory networksGene expression patternsRelated trypanosomatidsTranscriptional machineryCellular fateGene networksRegulatory networksTrypanosoma bruceiExpression patternsRegulatory mechanismsDifferent hostsRBPsLife cyclePathogenic organismsRNAOrganismsProteinDifferent environmentsCrucial role
2013
Genetically Distinct Glossina fuscipes fuscipes Populations in the Lake Kyoga Region of Uganda and Its Relevance for Human African Trypanosomiasis
Echodu R, Sistrom M, Hyseni C, Enyaru J, Okedi L, Aksoy S, Caccone A. Genetically Distinct Glossina fuscipes fuscipes Populations in the Lake Kyoga Region of Uganda and Its Relevance for Human African Trypanosomiasis. BioMed Research International 2013, 2013: 614721. PMID: 24199195, PMCID: PMC3807537, DOI: 10.1155/2013/614721.Peer-Reviewed Original ResearchConceptsSex-biased dispersalMicrosatellite DNA dataLack of admixtureAgents of humanVicariant barrierGenetic differentiationSouthern populationsDNA dataTrypanosoma bruceiCompetitive exclusionMain vector speciesSole vectorsContact zonePopulation clustersVector speciesEnvironmental conditionsTsetse fliesDistinct groupsAnimal trypanosomiasisHuman African trypanosomiasisGlossinaAfrican trypanosomiasisIntrogressionSympatryDispersal
2012
Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery
Barnes RL, Shi H, Kolev NG, Tschudi C, Ullu E. Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery. PLOS Pathogens 2012, 8: e1002678. PMID: 22654659, PMCID: PMC3359990, DOI: 10.1371/journal.ppat.1002678.Peer-Reviewed Original ResearchConceptsRNA interferenceT. bruceiComparative genomicsTrypanosoma bruceiMechanism of RNAiCatalog of genesCore RNAi machineryWide RNAi screenArgonaute 1 proteinNext-generation IlluminaRepertoire of factorsLoss of fitnessDistinct developmental stagesAncient eukaryotesRNAi factorsCore machineryRNAi machineryRNAi screenRNAi toolTrypanosomatid protozoaDuplex siRNAsRNAi efficiencyHuman parasitesMolecular explorationBrucei
2011
The RNA Interference Pathway in Trypanosoma brucei
Ullu E, Kolev N, Barnes R, Tschudi C. The RNA Interference Pathway in Trypanosoma brucei. Nucleic Acids And Molecular Biology 2011, 28: 167-185. DOI: 10.1007/978-3-642-28687-2_8.Peer-Reviewed Original ResearchRNA interference (RNAi) pathwayInterference pathwayEarly divergent eukaryoteMost eukaryotic cellsSequence-specific mannerEukaryotic evolutionDivergent eukaryotesHigher eukaryotesRNAi machineryEukaryotic cellsLong dsRNAsRNAi mechanismTarget transcriptsTrypanosoma bruceiConsequence cellsSpecific defense mechanismsEukaryotesProtozoan parasiteDefense mechanismsTranscriptsCurrent understandingNucleic acidsPathwayHighlight similaritiesSuch mechanisms
2010
The Transcriptome of the Human Pathogen Trypanosoma brucei at Single-Nucleotide Resolution
Kolev NG, Franklin JB, Carmi S, Shi H, Michaeli S, Tschudi C. The Transcriptome of the Human Pathogen Trypanosoma brucei at Single-Nucleotide Resolution. PLOS Pathogens 2010, 6: e1001090. PMID: 20838601, PMCID: PMC2936537, DOI: 10.1371/journal.ppat.1001090.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceGene Expression ProfilingGenome, BacterialHigh-Throughput Nucleotide SequencingHumansMolecular Sequence DataRNA Polymerase IIRNA PrecursorsRNA, BacterialSequence Homology, Nucleic AcidTranscription Initiation SiteTranscription, GeneticTrypanosoma brucei bruceiTrypanosomiasis, AfricanConceptsGene clusterNew transcriptsHigh-throughput RNA sequencingInitiation siteOrganization of genesRNA polymerase IISimilar genome organizationPutative initiation siteSingle-nucleotide resolutionTranscription initiation siteGene expression patternsPre-mRNA processingNon-coding RNAsGenome organizationPolymerase IIGenomic mapTranscription initiationInsect vectorsEukaryotic promotersMass spectrometry analysisImportant human pathogenMammalian hostsRNA sequencingTrypanosoma bruceiT. brucei
2009
Distinct and overlapping roles for two Dicer-like proteins in the RNA interference pathways of the ancient eukaryote Trypanosoma brucei
Patrick KL, Shi H, Kolev NG, Ersfeld K, Tschudi C, Ullu E. Distinct and overlapping roles for two Dicer-like proteins in the RNA interference pathways of the ancient eukaryote Trypanosoma brucei. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 17933-17938. PMID: 19815526, PMCID: PMC2764927, DOI: 10.1073/pnas.0907766106.Peer-Reviewed Original ResearchConceptsDicer-like enzymesRNA interferenceRNAi pathwayBiogenesis of siRNAsDicer-like proteinsNuclear RNAi pathwaySingle Argonaute proteinEnd modificationReverse genetic analysisRNAi-deficient cellsRNA interference (RNAi) pathwayWild-type cellsAncient eukaryotesArgonaute proteinsRNAi responseAncient traitRepeat transcriptsInterference pathwayCytoplasmic proteinsImportant human pathogenTrypanosoma bruceiGenetic analysisRNAi triggersFunctional analysisIntermediate transcripts
2007
Telomeric co-localization of the modified base J and contingency genes in the protozoan parasite Trypanosoma cruzi
Ekanayake D, Cipriano M, Sabatini R. Telomeric co-localization of the modified base J and contingency genes in the protozoan parasite Trypanosoma cruzi. Nucleic Acids Research 2007, 35: 6367-6377. PMID: 17881368, PMCID: PMC2095807, DOI: 10.1093/nar/gkm693.Peer-Reviewed Original ResearchConceptsTelomeric repeat sequencesBase JVariant surface glycoproteinRepeat sequencesGenes adjacent to telomeresExpression sitesAnalysis of DNA sequencesBeta-d-glucosylhydroxymethyluracilAdjacent to telomeresGene expression sitesSouth American trypanosomesSurface glycoprotein genesActive expression siteContingency genesSubtelomeric regionsTelomeric repeatsDNA sequencesAmerican trypanosomesDNA digestionTelomeric genesTrypanosoma bruceiSouthern blottingTelomere distributionKinetoplastid parasitesGlycoprotein gene
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