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
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
Multidisciplinary Sciences
Nurit Yaffe, Dvir Rotem, Awakash Soni, Danny Porath, Joseph Shlomai
Summary: This study focused on the condensation of kinetoplast DNA (kDNA), the mitochondrial genome of kinetoplastids, and revealed the role of the replication protein UMSBP in decondensation and initiation of kDNA replication. The condensation of kDNA was found to proceed through a series of hierarchical steps, with multiple local condensation foci assembling into higher order condensation centers, influenced by the maxicircles component of kDNA. The structure of condensing kDNA intermediates shed light on the organization of the condensed kDNA network within the mitochondrial nucleoid.
SCIENTIFIC REPORTS
(2021)
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
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
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
Microbiology
Anuj Tripathi, Ujjal K. Singha, Ayorinde Cooley, Taneisha Gillyard, Evan Krystofiak, Siddharth Pratap, Jamaine Davis, Minu Chaudhuri
Summary: TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and the cell cycle in the bloodstream form of T. brucei. Depletion of TbTim50 results in inhibited cell growth, changes in morphology, increased AMPK phosphorylation, and upregulation of stumpy marker genes. TbTim50 is a crucial therapeutic target for African trypanosomiasis.
Article
Multidisciplinary Sciences
Susanne Wegmann, Sarah L. DeVos, Bryan Zeitler, Kimberly Marlen, Rachel E. Bennett, Marta Perez-Rando, Danny MacKenzie, Qi Yu, Caitlin Commins, Riley N. Bannon, Bianca T. Corjuc, Alison Chase, Lisa Diez, Hoang-Oanh B. Nguyen, Sarah Hinkley, Lei Zhang, Alicia Goodwin, Annemarie Ledeboer, Stephen Lam, Irina Ankoudinova, Hung Tran, Nicholas Scarlott, Rainier Amora, Richard Surosky, Jeffrey C. Miller, Ashley B. Robbins, Edward J. Rebar, Fyodor D. Urnov, Michael C. Holmes, Amy M. Pooler, Brigit Riley, H. Steve Zhang, Bradley T. Hyman
Summary: The study demonstrates that reducing tau protein expression using gene-silencing technology can effectively rescue neuronal damage in an Alzheimer's disease model, with sustained effects and no detectable side effects. This approach shows promise for the treatment of tau-related human brain diseases.
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
Cell Biology
Anna C. Albisetti, Robert L. Douglas, Matthew D. Welch
Summary: This study reveals that the trypanosome-specific kinesin KIN-E is crucial for the assembly of the flagellum attachment zone (FAZ) in bloodstream-form Trypanosoma brucei. Depletion of KIN-E inhibits flagellum attachment and leads to cell death, with phenotypes including failure in cytokinesis completion, kinetoplast DNA missegregation, and transport vesicle accumulation.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Microbiology
Christina Wilkinson, Meredith T. Morris
Summary: This study demonstrates a complex relationship between FBPase activity and extracellular glucose levels in Trypanosoma brucei, suggesting a potential additional role for FBPase in parasite metabolism. The differential expression of FBPase in various parasite cell lines and growth conditions implies regulation via post-translational modifications. These findings provide new insights into the metabolic pathways of Trypanosoma brucei.
Article
Biochemistry & Molecular Biology
Lanjie Zhao, Youzhong Li, Yan Li, Wei Chen, Jinbo Yao, Shengtao Fang, Youjun Lv, Yongshan Zhang, Shouhong Zhu
Summary: The study identified GhDi19-3 and GhDi19-4 as negative transcription factors responsive to salt stress through calcium signaling and ABA signaling pathways.
Review
Biochemistry & Molecular Biology
Ruize Sun, Jue Wang, Juan Feng, Bin Cao
Summary: Zinc is an essential micronutrient for both plant and animal growth, playing a critical role in the development of the central nervous system. Zinc deficiency can lead to various diseases and pathological conditions, including cognitive impairment and premature aging. This study reviews the important effects of zinc in cognitive impairment and aging, explores its molecular mechanism, and highlights potential interventions for zinc-related aging and cognitive impairments.
Article
Biochemistry & Molecular Biology
Weijuan Xu, Shuguang Jian, Jianyi Li, Yusang Wang, Mingyong Zhang, Kuaifei Xia
Summary: Pitaya, a plant with tolerance to drought, heat, and poor soil, has gene expression and stress response regulated by zinc finger proteins. A total of 81 CCCH-type zinc finger protein genes were identified in the pitaya genome, and HuTZF3 was found to respond to both salt and heat stress. HuTZF3 showed expression in all tested organs of pitaya, especially with high levels in roots and stems, and its expression was induced by salt and heat stress. Subcellular localization revealed that HuTZF3 is targeted in processing bodies and stress granules. Heterologous expression of HuTZF3 in Arabidopsis improved salt and heat tolerance, reduced oxidative stress, and enhanced the activity of catalase and peroxidase. Thus, HuTZF3 may contribute to post-transcriptional regulation via its localization in processing bodies and stress granules, contributing to salt and heat tolerance in pitaya.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vianney Poignavent, Francois Hoh, Guillaume Terral, Yinshan Yang, Francois-Xavier Gillet, Jeong-Hyeon Kim, Frederic Allemand, Eric Lacombe, Christophe Brugidou, Sarah Cianferani, Helene Demene, Florence Vignols
Summary: Viruses of the sobemovirus genus, including the rice yellow mottle virus (RYMV), cause significant losses in agriculture. In this study, the complete 3D structure and dynamics of the P1 protein, responsible for RYMV infectivity, were determined. The P1 protein consists of two independent domains with distinct zinc fingers and different sensitivities to oxidoreduction conditions. The capacity of P1 to oligomerize and key residues essential for infectivity in rice tissues were also identified. These findings provide insights into RYMV functions and its interaction with the host plant.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Hematology
Manuel Montesinos-Rongen, Monica Terrao, Caroline May, Katrin Marcus, Ingmar Blumcke, Martin Hellmich, Ralf Kuppers, Anna Brunn, Martina Deckert
Summary: The mutational pattern of the B-cell receptor in PCNSL cells suggests antigenic selection and confinement in the CNS, supporting the pathogenesis of the disease. Abnormal GC reaction in PCNSL may increase self-/polyreactivity, facilitating BCR signaling via multiple CNS antigens and promoting tumor cell survival in the CNS.
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)