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Ares element in trypanosomatids

Sanofar Abdeen, Nilshad Salim, Najiba Mammadova, Corey M Summers, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Peter G Schultz, Arthur L Horwich, Eli Chapman, Steven M Johnson
Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival...
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
Dapeng Zhang, A Maxwell Burroughs, Newton D Vidal, Lakshminarayan M Iyer, L Aravind
Enzymatic effectors targeting nucleic acids, proteins and other cellular components are the mainstay of conflicts across life forms. Using comparative genomics we identify a large class of eukaryotic proteins, which include effectors from oomycetes, fungi and other parasites. The majority of these proteins have a characteristic domain architecture with one of several N-terminal 'Header' domains, which are predicted to play a role in trafficking of these effectors, including a novel version of the Ubiquitin fold...
May 5, 2016: Nucleic Acids Research
Mariana Bonilla, Erika Krull, Florencia Irigoín, Gustavo Salinas, Marcelo A Comini
The trace element selenium is found in polypeptides as selenocysteine, the 21(st) amino acid that is co-translationally inserted into proteins at a UGA codon. In proteins, selenocysteine usually plays a role as an efficient redox catalyst. Trypanosomatids previously examined harbor a full set of genes encoding the machinery needed for selenocysteine biosynthesis and incorporation into three selenoproteins: SelK, SelT and, the parasite-specific, Seltryp. We investigated the selenoproteome of kinetoplastid species in recently sequenced genomes and assessed the in vivo relevance of selenoproteins for African trypanosomes...
March 2016: Molecular and Biochemical Parasitology
Francisco Macías, Manuel Carlos López, M Carmen Thomas
BACKGROUND: Trypanosomatid genomes are highly colonized by non-LTR retroelements that make up to 5% of the nuclear genome. These elements are mainly accumulated in the strand switch regions (SSRs) where polycistronic transcription is initiated and have a 77 nt-long sequence--Pr77--at their 5' ends. L1Tc is the best represented retrotransposon in the Trypanosoma cruzi genome and is a potentially functional autonomous element that encodes its own retrotransposition machinery. The Pr77 of the T...
2016: BMC Genomics
Bhaskar Anand Jha, Vahid H Gazestani, Chun Wai Yip, Reza Salavati
DRBD13 RNA-binding protein (RBP) regulates the abundance of AU-rich element (ARE)-containing transcripts in trypanosomes. Here we show that DRBD13 regulates RBP6, the developmentally critical protein in trypanosomatids. We also show DRBD13-specific regulation of transcripts encoding cell surface coat proteins including GPEET2, variable surface glycoprotein (VSG) and invariant surface glycoprotein (ISG). Accordingly, alteration in DRBD13 levels leads to changes in the target mRNA abundance and parasite morphology...
July 8, 2015: FEBS Letters
Jennifer M Holden, Ludek Koreny, Steven Kelly, Brian T Chait, Michael P Rout, Mark C Field, Samson O Obado
The nuclear pore complex (NPC) is the sole mediator of bidirectional nucleo-cytoplasmic transport and is also an important scaffold for chromatin organization and transcriptional regulation. Proteomic studies of numerous diverse eukaryotic species initially characterized the NPC as built with a number of remarkably similar structural features, suggesting its status as an ancient and conserved eukaryotic cell component. However, further detailed analyses now suggest that several key specific NPC features have a more convoluted evolutionary history than initially assumed...
July 2014: Nucleus
Jeziel D Damasceno, Stephen M Beverley, Luiz R O Tosi
The ability of transposable elements to mobilize across genomes and affect the expression of genes makes them exceptional tools for genetic manipulation methodologies. Several transposon-based systems have been modified and incorporated into shuttle mutagenesis approaches in a variety of organisms. We have found that the Mos1 element, a DNA transposon from Drosophila mauritiana, is suitable and readily adaptable to a variety of strategies to the study of trypanosomatid parasitic protozoa. Trypanosomatids are the causative agents of a wide range of neglected diseases in underdeveloped regions of the globe...
2015: Methods in Molecular Biology
Frédéric Bringaud, Matthew Rogers, Elodie Ghedin
Transposable elements (TE), defined as discrete pieces of DNA that can move from one site to another site in genomes, represent significant components of eukaryotic genomes, including trypanosomatids. Up to 5% of the trypanosomatid genome content is composed of retroposons of the ingi clade, further divided into subclades and subfamilies ranging from short extinct truncated elements (SIDER) to long active elements (ingi). Important differences in ingi-related retroposon content have been reported between trypanosomatid species...
2015: Methods in Molecular Biology
Jennifer M Holden, Ludek Koreny, Steven Kelly, Brian T Chait, Michael P Rout, Mark C Field, Samson O Obado
The nuclear pore complex (NPC) is the sole mediator of bidirectional nucleo-cytoplasmic transport and is also an important scaffold for chromatin organization and transcriptional regulation. Proteomic studies of numerous diverse eukaryotic species initially characterized the NPC as built with a number of remarkably similar structural features, suggesting its status as an ancient and conserved eukaryotic cell component. However, further detailed analyses now suggest that several key specific NPC features have a more convoluted evolutionary history than initially assumed...
July 31, 2014: Nucleus
Esteban D Erben, Abeer Fadda, Smiths Lueong, Jörg D Hoheisel, Christine Clayton
In trypanosomatids, gene expression is regulated mainly by post-transcriptional mechanisms, which affect mRNA processing, translation and degradation. Currently, our understanding of factors that regulate either mRNA stability or translation is rather limited. We know that often, the regulators are proteins that bind to the 3'-untranslated region; they presumably interact with ribonucleases and translation factors. However, very few such proteins have been characterized in any detail. Here we describe a genome-wide screen to find proteins implicated in post-transcriptional regulation in Trypanosoma brucei...
June 2014: PLoS Pathogens
Francisco José Sánchez-Luque, Manuel Carlos López, Patricia Eugenia Carreira, Carlos Alonso, María Carmen Thomas
BACKGROUND: Hepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements in which they take part in a mechanism that releases intermediate RNAs from cellular co-transcripts. L1Tc in Trypanosoma cruzi is one of the elements in which such a ribozyme is located. It lies in the so-called Pr77-hallmark, a conserved region shared by retrotransposons belonging to the trypanosomatid L1Tc/ingi clade. The wide distribution of the Pr77-hallmark detected in trypanosomatid retrotransposons renders the potential catalytic activity of these elements worthy of study: their distribution might contribute to host genetic regulation at the mRNA level...
2014: BMC Genomics
Vahid H Gazestani, Zhiquan Lu, Reza Salavati
Morphological and metabolic changes in the life cycle of Trypanosoma brucei are accomplished by precise regulation of hundreds of genes. In the absence of transcriptional control, RNA-binding proteins (RBPs) shape the structure of gene regulatory maps in this organism, but our knowledge about their target RNAs, binding sites, and mechanisms of action is far from complete. Although recent technological advances have revolutionized the RBP-based approaches, the main framework for the RNA regulatory element (RRE)-based approaches has not changed over the last two decades in T...
May 2014: Trends in Parasitology
M T A da Silva, I Silva-Jardim, O H Thiemann
Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms...
2014: Current Medicinal Chemistry
Britta A Anderson, Iris L K Wong, Loren Baugh, Gowthaman Ramasamy, Peter J Myler, Stephen M Beverley
Regions of transcription initiation and termination in kinetoplastid protists lack known eukaryotic promoter and terminator elements, although epigenetic marks such as histone variants and the modified DNA base J have been localized to these regions in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major. Phenotypes of base J mutants vary significantly across trypanosomatids, implying divergence in the epigenetic networks governing transcription during evolution. Here, we demonstrate that the histone variants H2A...
October 2013: Molecular and Biochemical Parasitology
C A Ramírez, M A Dea-Ayuela, M D Gutiérrez-Blázquez, F Bolas-Fernández, J M Requena, C J Puerta
UNLABELLED: HSP70 protein is involved in Leishmania differentiation, apoptosis, antimony-resistance and host-immune response. Therefore, this protein and the regulatory mechanisms of HSP70 gene expression are promising targets for therapeutic intervention against leishmaniasis. The regulation of mRNA expression in trypanosomatids operates mostly through the interaction of trans-acting proteins, and elements located in the untranslated regions of mRNAs. The aim of this work was to identify protein factors interacting specifically with the Leishmania braziliensis HSP70 mRNAs...
December 6, 2013: Journal of Proteomics
João M P Alves, Cecilia C Klein, Flávia Maia da Silva, André G Costa-Martins, Myrna G Serrano, Gregory A Buck, Ana Tereza R Vasconcelos, Marie-France Sagot, Marta M G Teixeira, Maria Cristina M Motta, Erney P Camargo
BACKGROUND: Trypanosomatids of the genera Angomonas and Strigomonas live in a mutualistic association characterized by extensive metabolic cooperation with obligate endosymbiotic Betaproteobacteria. However, the role played by the symbiont has been more guessed by indirect means than evidenced. Symbiont-harboring trypanosomatids, in contrast to their counterparts lacking symbionts, exhibit lower nutritional requirements and are autotrophic for essential amino acids. To evidence the symbiont's contributions to this autotrophy, entire genomes of symbionts and trypanosomatids with and without symbionts were sequenced here...
2013: BMC Evolutionary Biology
Javier G De Gaudenzi, Santiago J Carmona, Fernán Agüero, Alberto C Frasch
In eukaryotic cells, a group of messenger ribonucleic acids (mRNAs) encoding functionally interrelated proteins together with the trans-acting factors that coordinately modulate their expression is termed a post-transcriptional regulon, due to their partial analogy to a prokaryotic polycistron. This mRNA clustering is organized by sequence-specific RNA-binding proteins (RBPs) that bind cis-regulatory elements in the noncoding regions of genes, and mediates the synchronized control of their fate. These recognition motifs are often characterized by conserved sequences and/or RNA structures, and it is likely that various classes of cis-elements remain undiscovered...
2013: PeerJ
Hamed S Najafabadi, Zhiquan Lu, Chad MacPherson, Vaibhav Mehta, Véronique Adoue, Tomi Pastinen, Reza Salavati
While regulatory programs are extensively studied at the level of transcription, elements that are involved in regulation of post-transcriptional processes are largely unknown, and methods for systematic identification of these elements are in early stages. Here, using a novel computational framework, we have integrated sequence information with several functional genomics data sets to characterize conserved regulatory programs of trypanosomatids, a group of eukaryotes that almost entirely rely on post-transcriptional processes for regulation of mRNA abundance...
October 2013: Nucleic Acids Research
Dong-Hyun Kim, Michael Peter Barrett
Mechanisms regulating gene expression in trypanosomatid protozoa differ significantly from those in other eukaryotes. Transcription of the genome appears to be more or less constitutive with the polyadenylation and trans-splicing of large polycistronic RNAs producing monocistronic RNAs whose translation may then depend upon information within their 3' untranslated regions (3'UTRs). Various 3'UTR sequences involved in life-cycle stage-dependent differential gene expression have been described. Moreover, several RNA-binding proteins have been implicated in regulating expression of these transcripts through altering either their stability or their ability to interact with ribosomes...
June 2013: Molecular Microbiology
Paulo H M Calixto, Mainá Bitar, Keila A M Ferreira, Odonírio Abrahão, Eliane Lages-Silva, Glória R Franco, Luis E Ramírez, André L Pedrosa
Trypanosoma rangeli is a hemoflagellate parasite which is able to infect humans. Distinct from Trypanosoma cruzi, the causative agent of Chagas disease, T. rangeli is non-pathogenic to the vertebrate host. The manner by which the T. rangeli interacts with the host is still unknown, but it certainly depends on the surface molecules. Major surface proteins (MSP) are GPI-anchored, zinc-dependent metalloproteases present in the surface of all trypanosomatids studied so far, which are implicated as virulence factors in pathogenic trypanosomatids, such as Leishmania spp and T...
August 2013: Journal of Molecular Modeling
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