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Pesquisa : D13.444.735.790.552.968 [Categoria DeCS]
Referências encontradas : 281 [refinar]
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  1 / 281 MEDLINE  
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[PMID]:28744787
[Au] Autor:Krchnáková Z; Krajcovic J; Vesteg M
[Ad] Endereço:Department of RNA Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
[Ti] Título:On the Possibility of an Early Evolutionary Origin for the Spliced Leader Trans-Splicing.
[So] Source:J Mol Evol;85(1-2):37-45, 2017 Aug.
[Is] ISSN:1432-1432
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Trans-splicing is a process by which 5'- and 3'-ends of two pre-RNA molecules transcribed from different sites of the genome can be joined together to form a single RNA molecule. The spliced leader (SL) trans-splicing is mediated by the spliceosome and it allows the replacement of 5'-end of pre-mRNA by 5'(SL)-end of SL-RNA. This form of splicing has been observed in many phylogenetically unrelated eukaryotes. Either the SL trans-splicing (SLTS) originated in the last eukaryotic common ancestor (LECA) (or even earlier) and it was lost in most eukaryotic lineages, or this mechanism of RNA processing evolved several times independently in various unrelated eukaryotic taxa. The bioinformatic comparisons of SL-RNAs from various eukaryotic taxonomic groups have revealed the similarities of secondary structures of most SL-RNAs and a relative conservation of their splice sites (SSs) and Sm-binding sites (SmBSs). We propose that such structural and functional similarities of SL-RNAs are unlikely to have evolved repeatedly many times. Hence, we favor the scenario of an early evolutionary origin for the SLTS and multiple losses of SL-RNAs in various eukaryotic lineages.
[Mh] Termos MeSH primário: Eucariotos/genética
Evolução Molecular
RNA Líder para Processamento/genética
Trans-Splicing
[Mh] Termos MeSH secundário: Eucariotos/metabolismo
Filogenia
Precursores de RNA/metabolismo
RNA Líder para Processamento/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (RNA Precursors); 0 (RNA, Spliced Leader)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171207
[Lr] Data última revisão:
171207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1007/s00239-017-9803-y


  2 / 281 MEDLINE  
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[PMID]:28582530
[Au] Autor:Philippe L; Pandarakalam GC; Fasimoye R; Harrison N; Connolly B; Pettitt J; Müller B
[Ad] Endereço:School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
[Ti] Título:An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly.
[So] Source:Nucleic Acids Res;45(14):8474-8483, 2017 Aug 21.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Spliced leader (SL) trans-splicing is a critical element of gene expression in a number of eukaryotic groups. This process is arguably best understood in nematodes, where biochemical and molecular studies in Caenorhabditis elegans and Ascaris suum have identified key steps and factors involved. Despite this, the precise details of SL trans-splicing have yet to be elucidated. In part, this is because the systematic identification of the molecules involved has not previously been possible due to the lack of a specific phenotype associated with defects in this process. We present here a novel GFP-based reporter assay that can monitor SL1 trans-splicing in living C. elegans. Using this assay, we have identified mutants in sna-1 that are defective in SL trans-splicing, and demonstrate that reducing function of SNA-1, SNA-2 and SUT-1, proteins that associate with SL1 RNA and related SmY RNAs, impairs SL trans-splicing. We further demonstrate that the Sm proteins and pICln, SMN and Gemin5, which are involved in small nuclear ribonucleoprotein assembly, have an important role in SL trans-splicing. Taken together these results provide the first in vivo evidence for proteins involved in SL trans-splicing, and indicate that continuous replacement of SL ribonucleoproteins consumed during trans-splicing reactions is essential for effective trans-splicing.
[Mh] Termos MeSH primário: Proteínas de Helminto/genética
RNA de Helmintos/genética
RNA Líder para Processamento/genética
Ribonucleoproteínas/genética
Trans-Splicing
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Sequência de Bases
Caenorhabditis elegans/genética
Caenorhabditis elegans/metabolismo
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Proteínas de Helminto/metabolismo
Microscopia de Fluorescência
Interferência de RNA
Precursores de RNA/genética
Precursores de RNA/metabolismo
RNA de Helmintos/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Líder para Processamento/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Ribonucleoproteínas/metabolismo
Ribonucleoproteínas Nucleares Pequenas/genética
Ribonucleoproteínas Nucleares Pequenas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Helminth Proteins); 0 (RNA Precursors); 0 (RNA, Helminth); 0 (RNA, Messenger); 0 (RNA, Spliced Leader); 0 (Ribonucleoproteins); 0 (Ribonucleoproteins, Small Nuclear); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx500


  3 / 281 MEDLINE  
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[PMID]:28391323
[Au] Autor:Roy SW
[Ad] Endereço:Department of Biology, San Francisco State University, San Francisco, CA.
[Ti] Título:Genomic and Transcriptomic Analysis Reveals Spliced Leader Trans-Splicing in Cryptomonads.
[So] Source:Genome Biol Evol;9(3):468-473, 2017 Mar 01.
[Is] ISSN:1759-6653
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Spliced leader trans-splicing (SLTS) is a poorly understood mechanism that is found in a diversity of eukaryotic lineages. In SLTS, a short RNA sequence is added near the 5' ends of the transcripts of protein-coding genes by a modified spliceosomal reaction. Available data suggest that SLTS has evolved many times, and might be more likely to evolve in animals. That SLTS might be more likely to evolve in the context of the generally complex transcriptomes characteristic of animals suggests the possibility that SLTS functions in gene regulation or transcriptome diversification, however no general novel function for SLTS is known. Here, I report SLTS in a lineage of cellularly complex unicellular eukaryotes. Cryptomonads are a group of eukaryotic algae that acquired photosynthetic capacity by secondary endosymbiosis of a red alga, and that retain a reduced copy of the nucleus of the engulfed alga. I estimate that at least one-fifth of genes in the model cryptomonad Guillardia theta and its relative Hanusia phi undergo SLTS. I show that hundreds of genes in G. theta generate alternative transcripts by SLTS at alternative sites, however I find little evidence for alternative protein production by alternative SLTS splicing. Interestingly, I find no evidence for substantial operon structure in the G. theta genome, in contrast to previous findings in other lineages with SLTS. These results extend SLTS to another major group of eukaryotes, and heighten the mystery of the evolution of SLTS and its association with cellular and transcriptomic complexity.
[Mh] Termos MeSH primário: Criptófitas/genética
RNA Líder para Processamento/genética
Trans-Splicing/genética
Transcriptoma/genética
[Mh] Termos MeSH secundário: Genômica
Filogenia
Simbiose/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Spliced Leader)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170410
[St] Status:MEDLINE
[do] DOI:10.1093/gbe/evx012


  4 / 281 MEDLINE  
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[PMID]:28069429
[Au] Autor:Cirovic O; Trikin R; Hoffmann A; Doiron N; Jakob M; Ochsenreiter T
[Ad] Endereço:Institute of Cell Biology, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences at the University of Bern, Switzerland.
[Ti] Título:The nuclear RNA binding protein RBP33 influences mRNA and spliced leader RNA abundance in Trypanosoma brucei.
[So] Source:Mol Biochem Parasitol;212:16-20, 2017 Mar.
[Is] ISSN:1872-9428
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:RNA recognition motif (RRM) containing proteins are important regulators of gene expression in trypanosomes. Here we expand our current knowledge on the exclusively nuclear localized RRM domain containing protein RBP33 of Trypanosoma brucei. Overexpression of RBP33 leads to a quick growth arrest in G2/M in bloodstream form cells likely due to an overall mRNA- and spliced leader abundance decrease while the ribosomal RNAs remain unaffected. The recombinant RBP33 binds to poly(A) and random sequence RNA in vitro confirming its role as a RNA binding protein. Finally super-resolution microscopy detects RBP33 in small punctae throughout the nucleus and surrounding the nucleolus, however the signal is depleted inside the nucleolus.
[Mh] Termos MeSH primário: Proteínas de Protozoários/metabolismo
RNA Mensageiro/genética
RNA de Protozoário
RNA Líder para Processamento/genética
Proteínas de Ligação a RNA/metabolismo
Trypanosoma brucei brucei/genética
Trypanosoma brucei brucei/metabolismo
[Mh] Termos MeSH secundário: Expressão Gênica
Ligação Proteica
Proteínas de Protozoários/genética
Proteínas de Ligação a RNA/genética
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protozoan Proteins); 0 (RNA, Messenger); 0 (RNA, Protozoan); 0 (RNA, Spliced Leader); 0 (RNA-Binding Proteins); 0 (Recombinant Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE


  5 / 281 MEDLINE  
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[PMID]:28043022
[Au] Autor:Zhuang Y; Yang F; Xu D; Chen H; Zhang H; Liu G
[Ad] Endereço:Key Laboratory of Marine Environment and Ecology, Ministry of Education,Ocean University of China, Qingdao 266100, China.
[Ti] Título:Spliced leader-based analyses reveal the effects of polycyclic aromatic hydrocarbons on gene expression in the copepod Pseudodiaptomus poplesia.
[So] Source:Aquat Toxicol;183:114-126, 2017 Feb.
[Is] ISSN:1879-1514
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Polycyclic aromatic hydrocarbons (PAHs) are a group of toxic and carcinogenic pollutants that can adversely affect the development, growth and reproduction of marine organisms including copepods. However, knowledge on the molecular mechanisms regulating the response to PAH exposure in marine planktonic copepods is limited. In this study, we investigated the survival and gene expression of the calanoid copepod Pseudodiaptomus poplesia upon exposure to two PAHs, 1, 2-dimethylnaphthalene (1, 2-NAPH) and pyrene. Acute toxicity responses resulted in 96-h LC of 788.98µgL and 54.68µgL for 1, 2-NAPH and pyrene, respectively. Using the recently discovered copepod spliced leader as a primer, we constructed full-length cDNA libraries from copepods exposed to sublethal concentrations and revealed 289 unique genes of diverse functions, including stress response genes and novel genes previously undocumented for this species. Eighty-three gene families were specifically expressed in PAH exposure libraries. We further analyzed the expression of seven target genes by reverse transcription-quantitative PCR in a time-course test with three sublethal concentrations. These target genes have primary roles in detoxification, oxidative defense, and signal transduction, and include different forms of glutathione S-transferase (GST), glutathione peroxidases (GPX), peroxiredoxin (PRDX), methylmalonate-semialdehyde dehydrogenase (MSDH) and ras-related C3 botulinum toxin substrate (RAC1). Expression stability of seven candidate reference genes were evaluated and the two most stable ones (RPL15 and RPS20 for 1, 2-NAPH exposure, RPL15 and EF1D for pyrene exposure) were used to normalize the expression levels of the target genes. Significant upregulation was detected in GST-T, GST-DE, GPX4, PRDX6 and RAC1 upon 1, 2-NAPH exposure, and GST-DE and MSDH upon pyrene exposure. These results indicated that the oxidative stress was induced and that signal transduction might be affected by PAH exposure in P. poplesia. However, gene upregulation was followed by a reduction in expression level towards 96h, indicating a threshold value of exposure time that leads to depressed gene expression. Prolonged exposure may cause dysfunction of detoxification and antioxidant machinery in P. poplesia. The transcriptional responses of GST-T, GPX2 and GPX4 upon pyrene exposure were minimal. Our results reveal the different sensitivity of P. poplesia to two PAHs at both the individual and transcriptional levels. As the first attempt, this study proved that copepod spliced leader is useful for obtaining full-length cDNA in P. poplesia exposed to PAHs and provided a valuable gene resource for this non-model species. This approach can be applied to other calanoid copepods exposed to various stressors, particularly under field conditions.
[Mh] Termos MeSH primário: Copépodes/efeitos dos fármacos
Naftalenos/toxicidade
Pirenos/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Copépodes/genética
DNA Complementar/genética
Expressão Gênica/efeitos dos fármacos
Biblioteca Gênica
Dose Letal Mediana
RNA Líder para Processamento/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Naphthalenes); 0 (Pyrenes); 0 (RNA, Spliced Leader); 0 (Water Pollutants, Chemical); 573-98-8 (1,2-dimethylnaphthalene); 9E0T7WFW93 (pyrene)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


  6 / 281 MEDLINE  
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[PMID]:27455303
[Au] Autor:Mueller N; Das AT; Berkhout B
[Ad] Endereço:Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. n.muller@amc.uva.nl.
[Ti] Título:A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal.
[So] Source:Viruses;8(7), 2016 Jul 21.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5' splice site (5'ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5'ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5'ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations.
[Mh] Termos MeSH primário: HIV-1/genética
Conformação de Ácido Nucleico
RNA Líder para Processamento/química
RNA Líder para Processamento/genética
RNA Viral/genética
[Mh] Termos MeSH secundário: Infecções por HIV/virologia
HIV-1/isolamento & purificação
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Spliced Leader); 0 (RNA, Viral)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160726
[St] Status:MEDLINE


  7 / 281 MEDLINE  
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[PMID]:27312952
[Au] Autor:Barbosa EG; Crisp A; Broadbent SE; Carrillo M; Boschetti C; Tunnacliffe A
[Ad] Endereço:Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom.
[Ti] Título:A functional difference between native and horizontally acquired genes in bdelloid rotifers.
[So] Source:Gene;590(1):186-91, 2016 Sep 15.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The form of RNA processing known as SL trans-splicing involves the transfer of a short conserved sequence, the spliced leader (SL), from a noncoding SL RNA to the 5' ends of mRNA molecules. SL trans-splicing occurs in several animal taxa, including bdelloid rotifers (Rotifera, Bdelloidea). One striking feature of these aquatic microinvertebrates is the large proportion of foreign genes, i.e. those acquired by horizontal gene transfer from other organisms, in their genomes. However, whether such foreign genes behave similarly to native genes has not been tested in bdelloids or any other animal. We therefore used a combination of experimental and computational methods to examine whether transcripts of foreign genes in bdelloids were SL trans-spliced, like their native counterparts. We found that many foreign transcripts contain SLs, use similar splice acceptor sequences to native genes, and are able to undergo alternative trans-splicing. However, a significantly lower proportion of foreign mRNAs contains SL sequences than native transcripts. This demonstrates a novel functional difference between foreign and native genes in bdelloids and suggests that SL trans-splicing is not essential for the expression of foreign genes, but is acquired during their domestication.
[Mh] Termos MeSH primário: Transferência Genética Horizontal
Genoma Helmíntico
RNA de Helmintos/genética
RNA Mensageiro/genética
RNA Líder para Processamento/genética
Rotíferos/genética
Trans-Splicing
[Mh] Termos MeSH secundário: Processamento Alternativo
Sequência de Aminoácidos
Animais
Evolução Biológica
Perfilação da Expressão Gênica
Ontologia Genética
Anotação de Sequência Molecular
RNA de Helmintos/metabolismo
RNA Mensageiro/metabolismo
RNA Líder para Processamento/metabolismo
Alinhamento de Sequência
Transcriptoma
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Helminth); 0 (RNA, Messenger); 0 (RNA, Spliced Leader)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170125
[Lr] Data última revisão:
170125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160618
[St] Status:MEDLINE


  8 / 281 MEDLINE  
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[PMID]:27161313
[Au] Autor:Hope R; Egarmina K; Voloshin K; Waldman Ben-Asher H; Carmi S; Eliaz D; Drori Y; Michaeli S
[Ad] Endereço:The Mina and Everard Goodman Faculty of Life Sciences.
[Ti] Título:Transcriptome and proteome analyses and the role of atypical calpain protein and autophagy in the spliced leader silencing pathway in Trypanosoma brucei.
[So] Source:Mol Microbiol;102(1):1-21, 2016 Oct.
[Is] ISSN:1365-2958
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Under persistent ER stress, Trypanosoma brucei parasites induce the spliced leader silencing (SLS) pathway. In SLS, transcription of the SL RNA gene, the SL donor to all mRNAs, is extinguished, arresting trans-splicing and leading to programmed cell death (PCD). In this study, we investigated the transcriptome following silencing of SEC63, a factor essential for protein translocation across the ER membrane, and whose silencing induces SLS. The proteome of SEC63-silenced cells was analyzed with an emphasis on SLS-specific alterations in protein expression, and modifications that do not directly result from perturbations in trans-splicing. One such protein identified is an atypical calpain SKCRP7.1/7.2. Co-silencing of SKCRP7.1/7.2 and SEC63 eliminated SLS induction due its role in translocating the PK3 kinase. This kinase initiates SLS by migrating to the nucleus and phosphorylating TRF4 leading to shut-off of SL RNA transcription. Thus, SKCRP7.1 is involved in SLS signaling and the accompanying PCD. The role of autophagy in SLS was also investigated; eliminating autophagy through VPS34 or ATG7 silencing demonstrated that autophagy is not essential for SLS induction, but is associated with PCD. Thus, this study identified factors that are used by the parasite to cope with ER stress and to induce SLS and PCD.
[Mh] Termos MeSH primário: Calpaína/metabolismo
RNA Líder para Processamento/metabolismo
Trypanosoma brucei brucei/genética
Trypanosoma brucei brucei/metabolismo
[Mh] Termos MeSH secundário: Apoptose/fisiologia
Autofagia/fisiologia
Retículo Endoplasmático/metabolismo
Inativação Gênica/fisiologia
Proteínas de Membrana Transportadoras/genética
Proteínas de Membrana Transportadoras/metabolismo
Fosforilação
Transporte Proteico
Proteoma
Proteínas de Protozoários/genética
Proteínas de Protozoários/metabolismo
Interferência de RNA
Processamento de RNA
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Líder para Processamento/antagonistas & inibidores
Transcriptoma
Trypanosoma brucei brucei/citologia
Resposta a Proteínas não Dobradas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (Proteome); 0 (Protozoan Proteins); 0 (RNA, Messenger); 0 (RNA, Spliced Leader); EC 3.4.22.- (Calpain)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160511
[St] Status:MEDLINE
[do] DOI:10.1111/mmi.13417


  9 / 281 MEDLINE  
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[PMID]:26954683
[Au] Autor:Badjatia N; Park SH; Ambrósio DL; Kirkham JK; Günzl A
[Ad] Endereço:Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
[Ti] Título:Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.
[So] Source:PLoS Pathog;12(3):e1005498, 2016 Mar.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In eukaryotes, cyclin-dependent kinases (CDKs) control the cell cycle and critical steps in gene expression. The lethal parasite Trypanosoma brucei, member of the phylogenetic order Kinetoplastida, possesses eleven CDKs which, due to high sequence divergence, were generically termed CDC2-related kinases (CRKs). While several CRKs have been implied in the cell cycle, CRK9 was the first trypanosome CDK shown to control the unusual mode of gene expression found in kinetoplastids. In these organisms, protein-coding genes are arranged in tandem arrays which are transcribed polycistronically. Individual mRNAs are processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. CRK9 ablation was lethal in cultured trypanosomes, causing a block of trans splicing before the first transesterification step. Additionally, CRK9 silencing led to dephosphorylation of RNA polymerase II and to hypomethylation of the SL cap structure. Here, we tandem affinity-purified CRK9 and, among potential CRK9 substrates and modifying enzymes, discovered an unusual tripartite complex comprising CRK9, a new L-type cyclin (CYC12) and a protein, termed CRK9-associated protein (CRK9AP), that is only conserved among kinetoplastids. Silencing of either CYC12 or CRK9AP reproduced the effects of depleting CRK9, identifying these proteins as functional partners of CRK9 in vivo. While mammalian cyclin L binds to CDK11, the CRK9 complex deviates substantially from that of CDK11, requiring CRK9AP for efficient CRK9 complex formation and autophosphorylation in vitro. Interference with this unusual CDK rescued mice from lethal trypanosome infections, validating CRK9 as a potential chemotherapeutic target.
[Mh] Termos MeSH primário: Quinases Ciclina-Dependentes/metabolismo
RNA Líder para Processamento/metabolismo
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Animais
Quinases Ciclina-Dependentes/genética
Ciclinas/genética
Ciclinas/metabolismo
Feminino
Camundongos
Camundongos Endogâmicos BALB C
Filogenia
Poliadenilação
Antígeno Nuclear de Célula em Proliferação/genética
Antígeno Nuclear de Célula em Proliferação/metabolismo
RNA Polimerase II/genética
RNA Polimerase II/metabolismo
Precursores de RNA/genética
Precursores de RNA/metabolismo
RNA Líder para Processamento/genética
Trans-Splicing/genética
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Cyclins); 0 (Proliferating Cell Nuclear Antigen); 0 (RNA Precursors); 0 (RNA, Spliced Leader); EC 2.7.11.22 (Cyclin-Dependent Kinases); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160309
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1005498


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[PMID]:26701154
[Au] Autor:Lima L; Espinosa-Álvarez O; Pinto CM; Cavazzana M; Pavan AC; Carranza JC; Lim BK; Campaner M; Takata CS; Camargo EP; Hamilton PB; Teixeira MM
[Ad] Endereço:Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Lineu Prestes, 1374, 05508-000, São Paulo, SP, Brazil. lulima@usp.br.
[Ti] Título:New insights into the evolution of the Trypanosoma cruzi clade provided by a new trypanosome species tightly linked to Neotropical Pteronotus bats and related to an Australian lineage of trypanosomes.
[So] Source:Parasit Vectors;8:657, 2015 Dec 23.
[Is] ISSN:1756-3305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bat trypanosomes are implicated in the evolution of the T. cruzi clade, which harbours most African, European and American trypanosomes from bats and other trypanosomes from African, Australian and American terrestrial mammals, including T. cruzi and T. rangeli, the agents of the American human trypanosomiasis. The diversity of bat trypanosomes globally is still poorly understood, and the common ancestor, geographical origin, and evolution of species within the T. cruzi clade remain largely unresolved. METHODS: Trypanosome sequences were obtained from cultured parasites and from museum archived liver/blood samples of bats captured from Guatemala (Central America) to the Brazilian Atlantic Coast. Phylogenies were inferred using Small Subunit (SSU) rRNA, glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH), and Spliced Leader (SL) RNA genes. RESULTS: Here, we described Trypanosoma wauwau n. sp. from Pteronotus bats (Mormoopidae) placed in the T. cruzi clade, then supporting the bat-seeding hypothesis whereby the common ancestor of this clade likely was a bat trypanosome. T. wauwau was sister to the clade T. spp-Neobats from phyllostomid bats forming an assemblage of trypanosome species exclusively of Noctilionoidea Neotropical bats, which was sister to an Australian clade of trypanosomes from indigenous marsupials and rodents, which possibly evolved from a bat trypanosome. T. wauwau was found in 26.5% of the Pteronotus bats examined, and phylogeographical analysis evidenced the wide geographical range of this species. To date, this species was not detected in other bats, including those that were sympatric or shared shelters with Pteronotus. T. wauwau did not develop within mammalian cells, and was not infective to Balb/c mice or to triatomine vectors of T. cruzi and T. rangeli. CONCLUSIONS: Trypanosoma wauwau n. sp. was linked to Pteronotus bats. The positioning of the clade T. wauwau/T.spp-Neobats as the most basal Neotropical bat trypanosomes and closely related to an Australian lineage of trypanosomes provides additional evidence that the T. cruzi clade trypanosomes likely evolved from bats, and were dispersed in bats within and between continents from ancient to unexpectedly recent times.
[Mh] Termos MeSH primário: Evolução Molecular
Variação Genética
Trypanosoma cruzi/classificação
Trypanosoma cruzi/genética
[Mh] Termos MeSH secundário: Animais
Austrália
Brasil
América Central
Quirópteros
Análise por Conglomerados
DNA de Protozoário/química
DNA de Protozoário/genética
DNA Ribossômico/química
DNA Ribossômico/genética
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética
Camundongos Endogâmicos BALB C
Dados de Sequência Molecular
Filogenia
RNA Ribossômico 18S/genética
RNA Líder para Processamento
Análise de Sequência de DNA
Homologia de Sequência
Trypanosoma cruzi/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Protozoan); 0 (DNA, Ribosomal); 0 (RNA, Ribosomal, 18S); 0 (RNA, Spliced Leader); EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating))
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151225
[St] Status:MEDLINE
[do] DOI:10.1186/s13071-015-1255-x



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