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[PMID]:29408405
[Au] Autor:Wang H; Park BS; Lim WA; Ki JS
[Ad] Endereço:Department of Biotechnology, Sangmyung University, Seoul 03016, South Korea.
[Ti] Título:CpMCA, a novel metacaspase gene from the harmful dinoflagellate Cochlodinium polykrikoides and its expression during cell death.
[So] Source:Gene;651:70-78, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Metacaspases (MCAs) are cysteine proteases that share sequence homology with caspases, and may play roles in programmed cell death (PCD). In the present study, we identified a novel MCA gene (CpMCA) from the red tide dinoflagellate Cochlodinium polykrikoides, and examined its molecular characteristics and gene expression in response to algicide-induced cell death. CpMCA cDNA is 1164 bp in length, containing a dinoflagellate spliced leader sequence (dinoSL), an 879-bp open reading frame (ORF), which codes for a 293-aa protein, and a poly (A) tail. Multi-sequence comparison indicated that CpMCA belongs to type I MCA, but it has a different structure at the N-terminal. Phylogenetic analysis showed that C. polykrikoides may have acquired the MCA gene from bacteria by means of horizontal gene transfer (HGT). In addition, expressions of CpMCA significantly increased following exposure to the common algicides copper sulfate and oxidizing chlorine, which trigger cell death in dinoflagellates, suggesting that CpMCA may be involved in cell death.
[Mh] Termos MeSH primário: Caspases/genética
Dinoflagelados/genética
[Mh] Termos MeSH secundário: Morte Celular/efeitos dos fármacos
Morte Celular/genética
DNA Complementar
DNA de Protozoário
Dinoflagelados/efeitos dos fármacos
Dinoflagelados/enzimologia
Expressão Gênica
Transferência Genética Horizontal
Genes Bacterianos
Genes de Protozoários
Herbicidas/farmacologia
Filogenia
Análise de Sequência de DNA
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (DNA, Protozoan); 0 (Herbicides); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  2 / 4408 MEDLINE  
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[PMID]:29220437
[Au] Autor:Torres F; Arias-Carrasco R; Caris-Maldonado JC; Barral A; Maracaja-Coutinho V; De Queiroz ATL
[Ad] Endereço:Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
[Ti] Título:LeishDB: a database of coding gene annotation and non-coding RNAs in Leishmania braziliensis.
[So] Source:Database (Oxford);2017, 2017 Jan 01.
[Is] ISSN:1758-0463
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Database URL: www.leishdb.com.
[Mh] Termos MeSH primário: Genes de Protozoários/genética
Leishmania braziliensis/genética
RNA não Traduzido/genética
Interface Usuário-Computador
[Mh] Termos MeSH secundário: Genômica
Internet
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Untranslated)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1093/database/bax047


  3 / 4408 MEDLINE  
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[PMID]:29326268
[Au] Autor:Cowell AN; Istvan ES; Lukens AK; Gomez-Lorenzo MG; Vanaerschot M; Sakata-Kato T; Flannery EL; Magistrado P; Owen E; Abraham M; LaMonte G; Painter HJ; Williams RM; Franco V; Linares M; Arriaga I; Bopp S; Corey VC; Gnädig NF; Coburn-Flynn O; Reimer C; Gupta P; Murithi JM; Moura PA; Fuchs O; Sasaki E; Kim SW; Teng CH; Wang LT; Akidil A; Adjalley S; Willis PA; Siegel D; Tanaseichuk O; Zhong Y; Zhou Y; Llinás M; Ottilie S; Gamo FJ; Lee MCS; Goldberg DE; Fidock DA; Wirth DF; Winzeler EA
[Ad] Endereço:School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92093, USA.
[Ti] Título:Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.
[So] Source:Science;359(6372):191-199, 2018 01 12.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Resistência a Medicamentos/genética
Genoma de Protozoário
Plasmodium falciparum/efeitos dos fármacos
Plasmodium falciparum/genética
[Mh] Termos MeSH secundário: Ativação Metabólica
Alelos
Variações do Número de Cópias de DNA
Evolução Molecular Direcionada
Resistência a Múltiplos Medicamentos/genética
Genes de Protozoários
Metabolômica
Mutação
Plasmodium falciparum/crescimento & desenvolvimento
Seleção Genética
Fatores de Transcrição/química
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1126/science.aan4472


  4 / 4408 MEDLINE  
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[PMID]:29206858
[Au] Autor:de Francisco P; Martín-González A; Turkewitz AP; Gutiérrez JC
[Ad] Endereço:Departamento de Microbiología-III, Facultad de Biología, Universidad Complutense de Madrid (UCM), Madrid, Spain.
[Ti] Título:Extreme metal adapted, knockout and knockdown strains reveal a coordinated gene expression among different Tetrahymena thermophila metallothionein isoforms.
[So] Source:PLoS One;12(12):e0189076, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metallothioneins (MT) constitute a superfamily of small cytosolic proteins that are able to bind metal cations through numerous cysteine (Cys) residues. Like other organisms the ciliate Tetrahymena thermophila presents several MT isoforms, which have been classified into two subfamilies (Cd- and Cu-metallothioneins). The main aim of this study was to examine the specific functions and transcriptional regulation of the five MT isoforms present in T. thermophila, by using several strains of this ciliate. After a laboratory evolution experiment over more than two years, three different T. thermophila strains adapted to extreme metal stress (Cd2+, Cu2+ or Pb2+) were obtained. In addition, three knockout and/or knockdown strains for different metallothionein (MT) genes were generated. These strains were then analyzed for expression of the individual MT isoforms. Our results provide a strong basis for assigning differential roles to the set of MT isoforms. MTT1 appears to have a key role in adaptation to Cd. In contrast, MTT2/4 are crucial for Cu-adaptation and MTT5 appears to be important for Pb-adaptation and might be considered as an "alarm" MT gene for responding to metal stress. Moreover, results indicate that likely a coordinated transcriptional regulation exists between the MT genes, particularly among MTT1, MTT5 and MTT2/4. MTT5 appears to be an essential gene, a first such report in any organism of an essential MT gene.
[Mh] Termos MeSH primário: Adaptação Fisiológica
Expressão Gênica
Metalotioneína/genética
Metais/toxicidade
Isoformas de Proteínas/genética
Tetrahymena thermophila/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Genes de Protozoários
Tetrahymena thermophila/genética
Tetrahymena thermophila/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Metals); 0 (Protein Isoforms); 9038-94-2 (Metallothionein)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189076


  5 / 4408 MEDLINE  
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[PMID]:28985216
[Au] Autor:Hussein HE; Bastos RG; Schneider DA; Johnson WC; Adham FK; Davis WC; Laughery JM; Herndon DR; Alzan HF; Ueti MW; Suarez CE
[Ad] Endereço:Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, United States of America.
[Ti] Título:The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction.
[So] Source:PLoS Negl Trop Dis;11(10):e0005965, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1α-B promoter. Comparison of in vitro growth between a hap2-KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis.
[Mh] Termos MeSH primário: Vetores Aracnídeos/parasitologia
Babesia bovis/genética
Babesia bovis/fisiologia
Genes de Protozoários
Proteínas de Protozoários/genética
Proteínas de Protozoários/metabolismo
Rhipicephalus/parasitologia
[Mh] Termos MeSH secundário: Animais
Babesia bovis/efeitos dos fármacos
Babesia bovis/crescimento & desenvolvimento
Bovinos/parasitologia
Eritrócitos/parasitologia
Feminino
Estágios do Ciclo de Vida
Fator 1 de Elongação de Peptídeos/genética
Regiões Promotoras Genéticas
Reprodução/efeitos dos fármacos
Reprodução/genética
Xanturenatos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptide Elongation Factor 1); 0 (Protozoan Proteins); 0 (Xanthurenates); 58LAB1BG8J (xanthurenic acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005965


  6 / 4408 MEDLINE  
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[PMID]:28938001
[Au] Autor:Chandra U; Yadav A; Kumar D; Saha S
[Ad] Endereço:Department of Microbiology, University of Delhi South Campus, New Delhi, India.
[Ti] Título:Cell cycle stage-specific transcriptional activation of cyclins mediated by HAT2-dependent H4K10 acetylation of promoters in Leishmania donovani.
[So] Source:PLoS Pathog;13(9):e1006615, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromatin modifications affect several processes. In investigating the Leishmania donovani histone acetyltransferase HAT2, using in vitro biochemical assays and HAT2-heterozygous genomic knockout we found the constitutively nuclear HAT2 acetylated histone H4K10 in vitro and in vivo. HAT2 was essential. HAT2-depleted cells displayed growth and cell cycle defects, and poor survival in host cells. Real time PCR and DNA microarray analyses, as well as rescue experiments, revealed that downregulation of cyclins CYC4 and CYC9 were responsible for S phase and G2/M defects of HAT2-depleted cells respectively. Leishmania genes are arranged in unidirectional clusters, and clustered genes are coordinately transcribed as long polycistronic units, typically from divergent strand switch regions (dSSRs) which initiate transcription bidirectionally on opposite strands. In investigating the mechanism by which CYC4 and CYC9 expression levels are reduced in HAT2-depleted cells without other genes in their polycistronic transcription units being coordinately downregulated, we found using reporter assays that CYC4 and CYC9 have their own specific promoters. Chromatin immunoprecipitation assays with H4acetylK10 antibodies and real time PCR analyses of RNA suggested these gene-specific promoters were activated in cell cycle-dependent manner. Nuclear run-on analyses confirmed that CYC4 and CYC9 were transcriptionally activated from their own promoters at specific cell cycle stages. Thus, there are two tiers of gene regulation. Transcription of polycistronic units primarily initiates at dSSRs, and this most likely occurs constitutively. A subset of genes have their own promoters, at least some of which are activated in a cell-cycle dependent manner. This second tier of regulation is more sensitive to H4K10 acetylation levels, resulting in downregulation of expression in HAT2-depleted cells. This report presents the first data pointing to cell cycle-specific activation of promoters in trypanosomatids, thus uncovering new facets of gene regulation in this parasite family.
[Mh] Termos MeSH primário: Ciclinas/genética
Genes de Protozoários/genética
Histonas/genética
Leishmania donovani/genética
Proteínas de Protozoários/genética
[Mh] Termos MeSH secundário: Acetilação
Imunoprecipitação da Cromatina
Regulação da Expressão Gênica
Leishmania donovani/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Regiões Promotoras Genéticas
Proteínas de Protozoários/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (Histones); 0 (Protozoan Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006615


  7 / 4408 MEDLINE  
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[PMID]:28802260
[Au] Autor:McDermott SM; Stuart K
[Ad] Endereço:Center for Infectious Disease Research (formerly Seattle BioMed), Seattle, Washington 98109, USA.
[Ti] Título:The essential functions of KREPB4 are developmentally distinct and required for endonuclease association with editosomes.
[So] Source:RNA;23(11):1672-1684, 2017 Nov.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in , and several transcripts are differentially edited in bloodstream (BF) and procyclic form (PF) cells correlating with changes in mitochondrial function. Editing is catalyzed by three ∼20S editosomes that have a common set of 12 proteins, but are typified by mutually exclusive RNase III KREN1, N2, and N3 endonucleases with distinct cleavage specificities. KREPB4 is a common editosome protein that has a degenerate RNase III domain lacking conserved catalytic residues, in addition to zinc-finger and Pumilio/fem-3 mRNA binding factor (PUF) motifs. Here we show that KREPB4 is essential for BF and PF growth, in vivo RNA editing, and editosome integrity, but that loss of KREPB4 has differential effects on editosome components and complexes between BF and PF cells. We used targeted mutagenesis to investigate the functions of the conserved PUF and RNase III domains in both life-cycle stages and show that the PUF motif is not essential for function in BF or PF. In contrast, specific mutations in the RNase III domain severely inhibit BF and PF growth and editing, and disrupt ∼20S editosomes, while others indicate that the RNase III domain is noncatalytic. We further show that KREPB4, specifically the noncatalytic RNase III domain, is required for the association of KREN1, N2, and N3 with PF editosomes. These results, combined with previous studies, support a model in which KREPB4 acts as a pseudoenzyme to form the noncatalytic half of an RNase III heterodimer with the editing endonucleases.
[Mh] Termos MeSH primário: Proteínas de Protozoários/metabolismo
Edição de RNA
Proteínas de Ligação a RNA/metabolismo
Trypanosoma brucei brucei/metabolismo
[Mh] Termos MeSH secundário: Endonucleases/metabolismo
Técnicas de Silenciamento de Genes
Genes de Protozoários
Modelos Biológicos
Mutação
Domínios Proteicos
Proteínas de Protozoários/química
Proteínas de Protozoários/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA de Protozoário/genética
RNA de Protozoário/metabolismo
Proteínas de Ligação a RNA/química
Proteínas de Ligação a RNA/genética
Ribonuclease III/química
Ribonuclease III/genética
Ribonuclease III/metabolismo
Trypanosoma brucei brucei/genética
Trypanosoma brucei brucei/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protozoan Proteins); 0 (RNA, Messenger); 0 (RNA, Protozoan); 0 (RNA-Binding Proteins); 0 (mitochondrial messenger RNA); EC 3.1.- (Endonucleases); EC 3.1.26.3 (Ribonuclease III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE
[do] DOI:10.1261/rna.062786.117


  8 / 4408 MEDLINE  
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[PMID]:28800609
[Au] Autor:Cámara MLM; Cánepa GE; Lantos AB; Balouz V; Yu H; Chen X; Campetella O; Mucci J; Buscaglia CA
[Ad] Endereço:Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECh), Universidad Nacional de San Martín (UNSAM) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
[Ti] Título:The Trypomastigote Small Surface Antigen (TSSA) regulates Trypanosoma cruzi infectivity and differentiation.
[So] Source:PLoS Negl Trop Dis;11(8):e0005856, 2017 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: TSSA (Trypomastigote Small Surface Antigen) is an antigenic, adhesion molecule displayed on the surface of Trypanosoma cruzi trypomastigotes. TSSA displays substantial sequence identity to members of the TcMUC gene family, which code for the trypomastigote mucins (tGPI-mucins). In addition, TSSA bears sequence polymorphisms among parasite strains; and two TSSA variants expressed as recombinant molecules (termed TSSA-CL and TSSA-Sy) were shown to exhibit contrasting features in their host cell binding and signaling properties. METHODS/PRINCIPLE FINDINGS: Here we used a variety of approaches to get insights into TSSA structure/function. We show that at variance with tGPI-mucins, which rely on their extensive O-glycoslylation to achieve their protective function, TSSA seems to be displayed on the trypomastigote coat as a hypo-glycosylated molecule. This has a functional correlate, as further deletion mapping experiments and cell binding assays indicated that exposition of at least two peptidic motifs is critical for the engagement of the 'adhesive' TSSA variant (TSSA-CL) with host cell surface receptor(s) prior to trypomastigote internalization. These motifs are not conserved in the 'non-adhesive' TSSA-Sy variant. We next developed transgenic lines over-expressing either TSSA variant in different parasite backgrounds. In strict accordance to recombinant protein binding data, trypomastigotes over-expressing TSSA-CL displayed improved adhesion and infectivity towards non-macrophagic cell lines as compared to those over-expressing TSSA-Sy or parental lines. These phenotypes could be specifically counteracted by exogenous addition of peptides spanning the TSSA-CL adhesion motifs. In addition, and irrespective of the TSSA variant, over-expression of this molecule leads to an enhanced trypomastigote-to-amastigote conversion, indicating a possible role of TSSA also in parasite differentiation. CONCLUSION/SIGNIFICANCE: In this study we provided novel evidence indicating that TSSA plays an important role not only on the infectivity and differentiation of T. cruzi trypomastigotes but also on the phenotypic variability displayed by parasite strains.
[Mh] Termos MeSH primário: Antígenos de Protozoários/química
Antígenos de Superfície/química
Mucinas/metabolismo
Trypanosoma cruzi/patogenicidade
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antígenos de Protozoários/genética
Antígenos de Superfície/genética
Diferenciação Celular
Cercopithecus aethiops
Doença de Chagas/parasitologia
Regulação da Expressão Gênica
Genes de Protozoários
Células HeLa
Seres Humanos
Proteínas Recombinantes/química
Trypanosoma cruzi/genética
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Antigens, Surface); 0 (Mucins); 0 (Recombinant Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005856


  9 / 4408 MEDLINE  
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[PMID]:28575287
[Au] Autor:Das A; Banday M; Fisher MA; Chang YJ; Rosenfeld J; Bellofatto V
[Ad] Endereço:Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
[Ti] Título:An essential domain of an early-diverged RNA polymerase II functions to accurately decode a primitive chromatin landscape.
[So] Source:Nucleic Acids Res;45(13):7886-7896, 2017 Jul 27.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A unique feature of RNA polymerase II (RNA pol II) is its long C-terminal extension, called the carboxy-terminal domain (CTD). The well-studied eukaryotes possess a tandemly repeated 7-amino-acid sequence, called the canonical CTD, which orchestrates various steps in mRNA synthesis. Many eukaryotes possess a CTD devoid of repeats, appropriately called a non-canonical CTD, which performs completely unknown functions. Trypanosoma brucei, the etiologic agent of African Sleeping Sickness, deploys an RNA pol II that contains a non-canonical CTD to accomplish an unusual transcriptional program; all protein-coding genes are transcribed as part of a polygenic precursor mRNA (pre-mRNA) that is initiated within a several-kilobase-long region, called the transcription start site (TSS), which is upstream of the first protein-coding gene in the polygenic array. In this report, we show that the non-canonical CTD of T. brucei RNA pol II is important for normal protein-coding gene expression, likely directing RNA pol II to the TSSs within the genome. Our work reveals the presence of a primordial CTD code within eukarya and indicates that proper recognition of the chromatin landscape is a central function of this RNA pol II-distinguishing domain.
[Mh] Termos MeSH primário: Proteínas de Protozoários/química
Proteínas de Protozoários/metabolismo
RNA Polimerase II/química
RNA Polimerase II/metabolismo
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Cromatina/genética
Cromatina/metabolismo
Expressão Gênica
Genes de Protozoários
Modelos Biológicos
Mutagênese Sítio-Dirigida
Domínios Proteicos
Proteínas de Protozoários/genética
RNA Polimerase II/genética
Precursores de RNA/genética
Precursores de RNA/metabolismo
RNA de Protozoário/genética
RNA de Protozoário/metabolismo
Coelhos
Sequências de Repetição em Tandem
Sítio de Iniciação de Transcrição
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (Protozoan Proteins); 0 (RNA Precursors); 0 (RNA, Protozoan); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx486


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[PMID]:28531310
[Au] Autor:Lu XM; Batugedara G; Lee M; Prudhomme J; Bunnik EM; Le Roch KG
[Ad] Endereço:Department of Cell Biology and Neuroscience, University of California, Riverside, CA, USA.
[Ti] Título:Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.
[So] Source:Nucleic Acids Res;45(13):7825-7840, 2017 Jul 27.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets.
[Mh] Termos MeSH primário: Genes de Protozoários
Plasmodium falciparum/genética
RNA de Protozoário/genética
[Mh] Termos MeSH secundário: Animais
Epigênese Genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento
Seres Humanos
Malária Falciparum/sangue
Malária Falciparum/parasitologia
Plasmodium falciparum/crescimento & desenvolvimento
Plasmodium falciparum/patogenicidade
Regiões Promotoras Genéticas
RNA Polimerase II/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA de Protozoário/metabolismo
Análise de Sequência de RNA
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (RNA, Protozoan); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx464



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