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Translate regulation in kinetoplastids

Céline Ronin, David Mendes Costa, Joana Tavares, Joana Faria, Fabrice Ciesielski, Paola Ciapetti, Terry K Smith, Jane MacDougall, Anabela Cordeiro-da-Silva, Iain K Pemberton
The de novo crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1 (LiSir2rp1) has been solved at 1.99Å in complex with an acetyl-lysine peptide substrate. The structure is broadly commensurate with Hst2/SIRT2 proteins of yeast and human origin, reproducing many of the structural features common to these sirtuin deacetylases, including the characteristic small zinc-binding domain, and the larger Rossmann-fold domain involved in NAD+-binding interactions. The two domains are linked via a cofactor binding loop ordered in open conformation...
2018: PloS One
Jason Carnes, Suzanne M McDermott, Kenneth Stuart
Editosomes are the multiprotein complexes that catalyze the insertion and deletion of uridines to create translatable mRNAs in the mitochondria of kinetoplastids. Recognition and cleavage of a broad diversity of RNA substrates in vivo require three functionally distinct RNase III-type endonucleases, as well as five additional editosome proteins that contain noncatalytic RNase III domains. RNase III domains have recently been identified in the editosome accessory proteins KREPB9 and KREPB10, suggesting a role related to editing endonuclease function...
January 2018: MSphere
Cornelia Klein, Monica Terrao, Christine Clayton
Kinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, with regulation of mRNA processing, translation and degradation by RNA-binding proteins. ZC3H32 is a cytosolic mRNA-binding protein with three non-canonical CCCH zinc finger domains. It is much more abundant in bloodstream-form Trypanosoma brucei than in procyclic forms. Tethering of ZC3H32 to a reporter mRNA suppressed translation and resulted in mRNA degradation, and deletion analysis suggested that this activity was present in both the N- and C-terminal domains, but not the central zinc finger-containing domain...
2017: PloS One
Henry M Kariithi, Sjef Boeren, Edwin K Murungi, Just M Vlak, Adly M M Abd-Alla
BACKGROUND: Glossina m. morsitans is the primary vector of the Trypanosoma brucei group, one of the causative agents of African trypanosomoses. The parasites undergo metacyclogenesis, i.e. transformation into the mammalian-infective metacyclic trypomastigote (MT) parasites, in the salivary glands (SGs) of the tsetse vector. Since the MT-parasites are largely uncultivable in vitro, information on the molecular processes that facilitate metacyclogenesis is scanty. METHODS: To bridge this knowledge gap, we employed tandem mass spectrometry to investigate protein expression modulations in parasitized (T...
August 2, 2016: Parasites & Vectors
C E Clayton
Kinetoplastid parasites adapt to different environments with wide-reaching control of gene expression, but transcription of nuclear protein-coding genes is polycistronic: there is no individual control of transcription initiation. Mature mRNAs are made by co-transcriptional trans splicing and polyadenylation, and competition between processing and nuclear degradation may contribute to regulation of mRNA levels. In the cytosol both the extent to which mRNAs are translated, and mRNA decay rates, vary enormously...
August 2016: Current Opinion in Microbiology
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
Narciso Couto, Jennifer Wood, Jill Barber
In this review article we examine the role of glutathione reductase in the regulation, modulation and maintenance of cellular redox homoeostasis. Glutathione reductase is responsible for maintaining the supply of reduced glutathione; one of the most abundant reducing thiols in the majority of cells. In its reduced form, glutathione plays key roles in the cellular control of reactive oxygen species. Reactive oxygen species act as intracellular and extracellular signalling molecules and complex cross talk between levels of reactive oxygen species, levels of oxidised and reduced glutathione and other thiols, and antioxidant enzymes such as glutathione reductase determine the most suitable conditions for redox control within a cell or for activation of programmed cell death...
June 2016: Free Radical Biology & Medicine
Javier G De Gaudenzi, Adriana V Jäger, Ronan Izcovich, Vanina A Campo
Trypanosomes regulate gene expression mostly by posttranscriptional mechanisms, including control of mRNA turnover and translation efficiency. This regulation is carried out via certain elements located at the 3'-untranslated regions of mRNAs, which are recognized by RNA-binding proteins. In trypanosomes, trans-splicing is of central importance to control mRNA maturation. We have previously shown that TcDRBD4/PTB2, a trypanosome homolog of the human polypyrimidine tract-binding protein splicing regulator, interacts with the intergenic region of one specific dicistronic transcript, referred to as TcUBP (and encoding for TcUBP1 and TcUBP2, two closely kinetoplastid-specific proteins)...
July 2016: Journal of Eukaryotic Microbiology
Gerald F Späth, Sima Drini, Najma Rachidi
Across bacterial, archaeal and eukaryotic kingdoms, heat shock proteins (HSPs) are defined as a class of highly conserved chaperone proteins that are rapidly induced in response to temperature increase through dedicated heat shock transcription factors. While this transcriptional response governs cellular adaptation of fungal, plant and animal cells to thermic shock and other forms of stress, early-branching eukaryotes of the kinetoplastid order, including trypanosomatid parasites, lack classical mechanisms of transcriptional regulation and show largely constitutive expression of HSPs, thus raising important questions on the function of HSPs in the absence of stress and the regulation of their chaperone activity in response to environmental adversity...
May 2015: Cellular Microbiology
C E Clayton
Regulation of gene expression in Kinetoplastids relies mainly on post-transcriptional mechanisms. Recent high-throughput analyses, combined with mathematical modelling, have demonstrated possibilities for transcript-specific regulation at every stage: trans splicing, polyadenylation, translation, and degradation of both the precursor and the mature mRNA. Different mRNA degradation pathways result in different types of degradation kinetics. The original idea that the fate of an mRNA - or even just its degradation kinetics - can be defined by a single "regulatory element" is an over-simplification...
July 2014: Molecular and Biochemical Parasitology
Eden R Freire, Ajay A Vashisht, Amaranta M Malvezzi, Joanna Zuberek, Gerasimos Langousis, Edwin A Saada, Janaína De F Nascimento, Janusz Stepinski, Edward Darzynkiewicz, Kent Hill, Osvaldo P De Melo Neto, James A Wohlschlegel, Nancy R Sturm, David A Campbell
Members of the eIF4E mRNA cap-binding family are involved in translation and the modulation of transcript availability in other systems as part of a three-component complex including eIF4G and eIF4A. The kinetoplastids possess four described eIF4E and five eIF4G homologs. We have identified two new eIF4E family proteins in Trypanosoma brucei, and define distinct complexes associated with the fifth member, TbEIF4E5. The cytosolic TbEIF4E5 protein binds cap 0 in vitro. TbEIF4E5 was found in association with two of the five TbEIF4Gs...
August 2014: RNA
Radika Soysa, Nicola S Carter, Phillip A Yates
Gene expression in kinetoplastid parasites is regulated via post-transcriptional mechanisms that modulate mRNA turnover, translation rate, and/or post-translational protein stability. To facilitate the analysis of post-transcriptional regulation, a dual luciferase system was developed in which firefly and Renilla luciferase reporters genetically fused to compatible drug resistance genes are integrated in place of one allele of the gene of interest and of an internal control gene, respectively, in a manner that preserves the cognate pre-mRNA processing signals...
June 2014: Molecular and Biochemical Parasitology
Huiqing Hu, Zhonglian Yu, Yi Liu, Tao Wang, Ying Wei, Ziyin Li
The chromosomal passenger complex (CPC) in animals, consisting of Aurora B kinase and three evolutionarily conserved proteins, plays crucial roles in mitosis and cytokinesis. However, Trypanosoma brucei expresses an unusual CPC consisting of an Aurora-like kinase, TbAUK1, and two kinetoplastid-specific proteins, TbCPC1 and TbCPC2. Despite their essential functions, little is known about the regulation of TbAUK1 and the roles of TbCPC1 and TbCPC2. Here, we investigate the effect of post-translational modification on the activity and spatiotemporal control of TbAUK1, and demonstrate that phosphorylation of two conserved threonine residues in the activation loop of the kinase domain contributes to TbAUK1 activation and function...
January 2014: Molecular Microbiology
Michel Pelletier, Alyssa S Frainier, Dominic N Munini, Jenna M Wiemer, Amber R Karpie, Jeff J Sattora
BACKGROUND: Arginine methylation is a post-translational modification that expands the functional diversity of proteins. Kinetoplastid parasites contain a relatively large group of protein arginine methyltransferases (PRMTs) compared to other single celled eukaryotes. Several T. brucei proteins have been shown to serve as TbPRMT substrates in vitro, and a great number of proteins likely to undergo methylation are predicted by the T. brucei genome. This indicates that a large number of proteins whose functions are modulated by arginine methylation await discovery in trypanosomes...
May 8, 2013: BMC Microbiology
Yaser Hashem, Amedee des Georges, Jie Fu, Sarah N Buss, Fabrice Jossinet, Amy Jobe, Qin Zhang, Hstau Y Liao, Robert A Grassucci, Chandrajit Bajaj, Eric Westhof, Susan Madison-Antenucci, Joachim Frank
Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments...
February 21, 2013: Nature
Susanne Kramer, Bridget Bannerman-Chukualim, Louise Ellis, Elizabeth A Boulden, Steve Kelly, Mark C Field, Mark Carrington
The number of paralogs of proteins involved in translation initiation is larger in trypanosomes than in yeasts or many metazoan and includes two poly(A) binding proteins, PABP1 and PABP2, and four eIF4E variants. In many cases, the paralogs are individually essential and are thus unlikely to have redundant functions although, as yet, distinct functions of different isoforms have not been determined. Here, trypanosome PABP1 and PABP2 have been further characterised. PABP1 and PABP2 diverged subsequent to the differentiation of the Kinetoplastae lineage, supporting the existence of specific aspects of translation initiation regulation...
2013: PloS One
J Clos, S Brandau, C Hoyer
The cellular heat shock response in kinetoplastid protozoa is regulated exclusively at a post-transcriptional level. The heat-inducibility of heat shock protein synthesis is retained under actinomycin C(1) which indicates an inducible translation of heat shock mRNAs. We have also assessed the ability of various chemicals known to be effective triggers of the heat shock response in higher eukaryotes to induce heat shock protein synthesis in Leishmania donovani. None of the tested chemicals elicited a stress response...
May 1998: Protist
Susanne Kramer
Kinetoplastids, including the human pathogens Trypanosoma brucei, Trypanosoma cruzi and Leishmania, are the only known organisms that do not regulate the transcription of protein coding genes transcribed by RNA polymerase II. Yet, profound changes in gene expression are induced by many different external stimuli and stresses, the extreme example are cascades of changes in gene expression initiated by differentiation triggers that ultimately and irreversibly result in the massive morphological and metabolic changes observed during life-cycle progression...
February 2012: Molecular and Biochemical Parasitology
Feng Li, Jeremy Herrera, Sharleen Zhou, Dmitri A Maslov, Larry Simpson
Uridine insertion/deletion RNA editing in kinetoplastid mitochondria corrects encoded frameshifts in mRNAs. The genetic information for editing resides in small guide RNAs (gRNAs), which form anchor duplexes just downstream of an editing site and mediate editing within a single editing "block." Many mRNAs require multiple gRNAs; the observed overall 3' to 5' polarity of editing is determined by the formation of upstream mRNA anchors by downstream editing. Hel61, a mitochondrial DEAD-box protein, was previously shown to be involved in RNA editing, but the functional role was not clear...
March 1, 2011: Proceedings of the National Academy of Sciences of the United States of America
Balázs Szöör
Protein phosphorylation is one of the most important post-translational modifications regulating various signaling processes in all known living organisms. In the cell, protein phosphatases and protein kinases play a dynamic antagonistic role, controlling the phosphorylation state of tyrosine (Tyr), serine (Ser) and threonine (Thr) side chains of proteins. The reversible phosphorylation modulates protein function, through initiating conformational changes, which influences protein complex formation, alteration of enzyme activity and changes in protein stability and subcellular localization...
October 2010: Molecular and Biochemical Parasitology
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