Article
Microbiology
Carla Gilabert Carbajo, Lucy J. Cornell, Youssef Madbouly, Zhihao Lai, Phillip A. Yates, Michele Tinti, Calvin Tiengwe
Summary: Iron deprivation in Trypanosoma brucei induces upregulation of TfR, parasite-specific genes, glucose uptake and glycolysis genes, endocytosis genes, and a divergent RNA binding protein RBP5. Cells depleted of TfR import free iron as a survival strategy. RBP5 expression is regulated post-transcriptionally and above a certain threshold is toxic, affecting cell cycle progression. This study sheds new light on the mechanisms by which T. brucei handles iron stress.
Article
Immunology
Yan-Zi Wen, Hao-Tian Tang, Xiao-Li Cai, Na Wu, Jia-Zhen Xu, Bi-Xiu Su, Geoff Hide, Zhao-Rong Lun, De-Hua Lai
Summary: In this study, PAG3 was identified as a key nuclear gene involved in the slender to stumpy differentiation pathway of Trypanosoma brucei in the mammalian host. The loss of this gene might explain the inability of T. evansi and some T. equiperdum to differentiate and the adaptation to transmission cycles that bypass the tsetse vector or mechanical contact.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Joseph T. Smith Jr, Brianna Tylec, Arunasalam Naguleswaran, Isabel Roditi, Laurie K. Read
Summary: This study reveals the importance of mitochondrial mRNA editing in the developmental regulation of Trypanosoma brucei. The researchers found that temperature reduction and depletion of the differentiation-repressive kinase RDK1 can affect the metabolism of Trypanosoma brucei by altering the editing of mitochondrial cytochrome mRNAs.
Article
Microbiology
Georgina Awuah-Mensah, Jennifer McDonald, Pieter C. Steketee, Delphine Autheman, Sarah Whipple, Simon D'Archivio, Cordelia Brandt, Simon Clare, Katherine Harcourt, Gavin J. Wright, Liam J. Morrison, Catarina Gadelha, Bill Wickstead
Summary: Animal African trypanosomiasis (AAT) is a severe, wasting disease affecting domestic livestock and diverse wildlife, predominantly caused by Trypanosoma congolense and T. vivax. However, due to challenges in genetic modifications, research on the pathogenic stages is limited, hindering the understanding of these parasites' biology. The development of tools for T. congolense, including gene tagging, knockout, transgene expression, and inducible gene knockdown, will greatly aid in further research on AAT and T. congolense biology.
Article
Parasitology
Esteban Erben, Kevin Leiss, Bin Liu, Diana Inchaustegui Gil, Claudia Helbig, Christine Clayton
Summary: Trypanosoma brucei relies heavily on mRNA-binding proteins to control mRNA fate due to the lack of individual promoters for its protein-coding genes. Specific RNA-binding proteins like ZC3H22, RBP9, and DRBD7 play crucial roles in regulating gene expression and cell growth in different life stages of the parasite. Proteins that prefer long mRNAs may have short or degenerate binding sites, and binding preferences for certain nucleotides can affect untranslated regions.
Article
Biochemistry & Molecular Biology
Srinivasan Ramakrishnan, Rodrigo P. Baptista, Beejan Asady, Guozhong Huang, Roberto Docampo
Summary: In Trypanosoma brucei, down-regulation of Vps41 expression through RNAi leads to significant inhibition of endocytosis, affecting cell growth, while other functions of Vps41 in mammalian and yeast cells remain unaffected. The essentiality of TbVps41 suggests it as a potential drug target.
Article
Multidisciplinary Sciences
Emma M. Briggs, Federico Rojas, Richard McCulloch, Keith R. Matthews, Thomas D. Otto
Summary: This study models the developmental steps of Trypanosoma brucei using oligopeptide-induced differentiation in vitro, capturing the transcriptomes of parasites through single cell transcriptomics. It details the relative order of biological events during asynchronous development, profiles dynamic gene expression patterns, identifies putative regulators, and provides a paradigm for dissecting differentiation events in parasites.
NATURE COMMUNICATIONS
(2021)
Article
Parasitology
Tania Bishola, Christine Clayton
Summary: In Trypanosoma brucei, ZC3H28 protein plays a vital role in stabilizing specific mRNAs and increasing protein levels. Mass spectrometry revealed that ZC3H28 is associated with ribosomal proteins, various RNA-binding proteins, and is involved in regulating long and poorly translated mRNAs.
Article
Infectious Diseases
Monica Chandra, Sara Dakovic, Konstantina Foti, Johan P. Zeelen, Monique van Straaten, Francisco Aresta-Branco, Eliane Tihon, Nicole Luebbehusen, Thomas Ruppert, Lucy Glover, F. Nina Papavasiliou, C. Erec Stebbins
Summary: African trypanosomes use antigenic variation of the VSG coat to evade host immunity. The metacyclic VSGs, expressed in the tsetse fly, were thought to be specialized. However, our study shows that they are similar to bloodstream form VSGs, suggesting they may not be suitable for vaccine development.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Pavan Kumar Kakumani, Yunkoo Ko, Sushmitha Ramakrishna, Grace Christopher, Maria Dodgson, Jatin Shrinet, Louis-Mathieu Harvey, Chanseok Shin, Martin J. Simard
Summary: This study found that the RNA binding protein CSDE1 controls the expression of miR-451 in erythroleukemia cells by binding to it. CSDE1 regulates the processing of pre-miR-451 by AGO2 through its N-terminal domains. CSDE1 also interacts with PARN to promote the trimming of intermediate miR-451 to its mature length. These results demonstrate that CSDE1 promotes the biogenesis of miR-451 in erythroid progenitors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Matilda Rehn, Anne Wenzel, Anne-Katrine Frank, Mikkel Bruhn Schuster, Sachin Pundhir, Nanna Jorgensen, Kristoffer Vitting-Seerup, Ying Ge, Johan Jendholm, Magali Michaut, Erwin M. Schoof, Tanja Lyholm Jensen, Nicolas Rapin, Russell T. Sapio, Kasper Langebjerg Andersen, Anders H. Lund, Michele Solimena, Martin Holzenberger, Dimitri G. Pestov, Bo Torben Porse
Summary: Ribosomopathies are a range of disorders that affect protein synthesis and primarily impact hematopoietic stem cells and erythroid development. This study demonstrates that the deletion of poly-pyrimidine-tract-binding protein 1 (PTBP1) in the hematopoietic compartment leads to a condition resembling ribosomopathy. The loss of PTBP1 results in reduced HSC self-renewal, erythroid differentiation, and protein synthesis, along with defects in splicing and ribosome biogenesis.
Article
Biochemistry & Molecular Biology
Cecilia Ortiz, Francesca Moraca, Marc Laverriere, Allan Jordan, Niall Hamilton, Marcelo A. Comini
Summary: G6PDH plays a crucial role in cell physiology by catalyzing the synthesis of NADPH(+) and ribose 5-phosphate. The study discovered that 16 alpha-brominated epiandrosterone is the most potent inhibitor of G6PDH in trypanosomatids. Further investigations showed that bromination at position 16 alpha of androstane derivatives yielded more potent T. cruzi G6PDH inhibitors.
Article
Parasitology
Gloria Ceballos-Perez, Miriam Rico-Jimenez, Claudia Gomez-Linan, Antonio M. Estevez
Summary: The zinc finger proteins ZC3H41 and Z41AP play crucial roles in controlling the fate of ribosomal components in response to environmental cues. They interact with multiple proteins and mRNAs, and their binding to target transcripts is weakened under nutritional stress, leading to the accumulation of 5S rRNA precursors and a decrease in protein translation.
PARASITES & VECTORS
(2023)
Article
Microbiology
Gergana Taleva, Michaela Husova, Brian Panicucci, Carolina Hierro-Yap, Erika Pineda, Marc Biran, Martin Moos, Petr Simek, Falk Butter, Frederic Bringaud, Alena Zikova
Summary: The long slender bloodstream form Trypanosoma brucei is capable of generating ATP through substrate-level phosphorylation pathways, providing necessary mitochondrial membrane potential. The ATP/ADP carrier (AAC) plays a role in this process.
Article
Cell Biology
Eliane Tihon, Karinna Rubio-Pena, Annick Dujeancourt-Henry, Aline Crouzols, Brice Rotureau, Lucy Glover
Summary: The life cycle of Trypanosoma brucei alternates between the tsetse fly vector and the mammalian host, and the infectivity to the host depends on the expression of metacyclic variant surface glycoprotein genes. This study reveals the role of VEX1 in the metacyclic differentiation process and its impact on the infectivity of T. brucei to mammalian hosts.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bin Liu, Kevin Kamanyi Marucha, Christine Clayton
MOLECULAR MICROBIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Kathrin Bajak, Kevin Leiss, Christine Clayton, Esteban Erben
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Larissa Melo do Nascimento, Monica Terrao, Kevin Kamanyi Marucha, Bin Liu, Franziska Egler, Christine Clayton
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Parasitology
K. Kamanyi Marucha, C. Clayton
Article
Parasitology
Esteban Erben, Kevin Leiss, Bin Liu, Diana Inchaustegui Gil, Claudia Helbig, Christine Clayton
Summary: Trypanosoma brucei relies heavily on mRNA-binding proteins to control mRNA fate due to the lack of individual promoters for its protein-coding genes. Specific RNA-binding proteins like ZC3H22, RBP9, and DRBD7 play crucial roles in regulating gene expression and cell growth in different life stages of the parasite. Proteins that prefer long mRNAs may have short or degenerate binding sites, and binding preferences for certain nucleotides can affect untranslated regions.
Article
Biology
Larissa Melo do Nascimento, Franziska Egler, Katharina Arnold, Nina Papavasiliou, Christine Clayton, Esteban Erben
Summary: The study identified CFB2 as a crucial protein for stabilizing VSG mRNA, described cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identified trans-acting factors present in the VSG messenger ribonucleoprotein particle, and mechanistically explained how CFB2 stabilizes the mRNA of this key pathogenicity factor. The approach used in this study has the potential to provide detailed biological insight into the metabolism of relatively abundant mRNAs in any eukaryote.
Article
Infectious Diseases
Julius Mulindwa, Geofrey Ssentamu, Enock Matovu, Kevin Kamanyi Marucha, Francisco Aresta-Branco, Claudia Helbig, Christine Clayton
Summary: Most researchers studying protist parasites use a limited number of laboratory-adapted isolates obtained decades ago, with little study on the effects of laboratory passages and in vitro culture adaptation. This study introduces two new strains of Trypanosoma brucei brucei, MAK65 and MAK98, showing changes in gene copy numbers during adaptation to culture. Trisomy and increased chromosome segments were observed in established cultured lines, providing useful strains for research on trypanosome differentiation and pathogenicity.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Parasitology
Tania Bishola, Christine Clayton
Summary: In Trypanosoma brucei, ZC3H28 protein plays a vital role in stabilizing specific mRNAs and increasing protein levels. Mass spectrometry revealed that ZC3H28 is associated with ribosomal proteins, various RNA-binding proteins, and is involved in regulating long and poorly translated mRNAs.
Article
Multidisciplinary Sciences
Franziska Falk, Kevin Kamanyi Marucha, Christine Clayton
Summary: Transcription in Trypanosoma brucei is mainly constitutive and polycistronic, relying on post-transcriptional mechanisms for gene expression control. EIF4E1 and 4EIP play crucial roles in regulating gene expression and parasite morphology transitions, while the relationship between TUT3 and 4EIP function remains unclear.
Article
Infectious Diseases
Tania Bishola Tshitenge, Lena Reichert, Bin Liu, Christine Clayton
Summary: This study demonstrates the developmental regulation of RBP10 and PGKC proteins in Trypanosoma brucei, which is essential for the parasite's growth and survival. The researchers identified six regulatory regions in the 3'-untranslated region of RBP10 mRNA and two independent regions in the 3'-untranslated region of PGKC mRNA that are responsible for developmental regulation. Despite the absence of obvious sequence similarities in these regulatory regions, trypanosome mRNAs have multiple regulatory sequences, potentially acting as a fail-safe mechanism to ensure correct regulation.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Tania Bishola Tshitenge, Christine Clayton
Summary: The RNA-binding protein DRBD18 in Trypanosoma brucei is involved in the export and processing of mRNA through binding to polypyrimidine tract motifs in the 3'-untranslated regions of mRNA precursors.
Article
Biology
Bin Liu, Christine Clayton
Summary: The study found that T. brucei RBP10 targets specific mRNAs for destruction and may be related to the UA(U)(6) motif. In vitro binding experiments showed that RBP10 does not distinguish between UA(U)(6) and UACUCUCU motifs.
BMC RESEARCH NOTES
(2022)
Article
Biochemistry & Molecular Biology
Franziska Falk, Rafael Melo Palhares, Albina Waithaka, Christine Clayton
Summary: In this study, the functions of different versions of the cap-binding translation initiation factor EIF4E in Trypanosoma brucei were investigated. It was found that EIF4E2 is associated with the RNA-binding protein SLBP2 in bloodstream forms, while EIF4E5 has no impact on growth and differentiation. Additionally, EIF4E2 is strongly associated with a subset of mRNAs that are maximally abundant in the S-phase, with their abundances decreased in EIF4E2 knock-out cells.
MOLECULAR MICROBIOLOGY
(2022)
Article
Infectious Diseases
Albina Waithaka, Olena Maiakovska, Dirk Grimm, Larissa Melo do Nascimento, Christine Clayton
Summary: This study describes a trans splicing reporter system that can be used for studying and screening the roles of sequences and proteins in mRNA processing. The results suggest that splice factor and SR-domain proteins may play key roles in splice site definition.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Marion Wargnies, Nicolas Plazolles, Robin Schenk, Oriana Villafraz, Jean-William Dupuy, Marc Biran, Sabine Bachmaier, Helene Baudouin, Christine Clayton, Michael Boshart, Frederic Bringaud
Summary: Trypanosomatids rearrange their genome using repeated sequences, impacting gene dosage and selecting adaptive traits to environmental pressure. In a specific example with PEPCK gene knockout, a rearrangement between two FRD genes produced a nonfunctional chimeric gene. This rearrangement led to growth impairment, suggesting a role for FRD in production of ROS.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)