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Pesquisa : G02.111.760.700 [Categoria DeCS]
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[PMID]:29287879
[Au] Autor:Niu Z; Yan D; Bressler S; Mei L; Feng Y; Liu X
[Ad] Endereço:Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
[Ti] Título:A novel splicing mutation in SMPX is linked to nonsyndromic progressive hearing loss.
[So] Source:Int J Pediatr Otorhinolaryngol;104:47-50, 2018 Jan.
[Is] ISSN:1872-8464
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: X-linked nonsyndromic hearing impairment is the rarest form of genetic hearing loss and represents only a minor fraction of all cases. The aim of this study was to investigate the cause of X-linked nonsyndromic sensorineural hearing loss in a three-generation American family. METHODS: Whole-exome sequencing and co-segregation analysis were used to identify disease-causing genes. RESULTS: In this study, we described in detail the clinical characteristics of the family and identified a novel frameshift mutation creating a premature stop codon (c.133-1 G > A, p.(Gly45fs*36)) of SMPX. The loss-of-function mutation was co-segregated with the progressive hearing loss phenotype and was absent in 200 normal controls. CONCLUSIONS: We report the first SMPX (DFNX4) mutation in a North American family. Our findings contribute to the existing genotypic and phenotypic spectrum of SMPX associated hearing loss. Furthermore, our data suggest that exome sequencing is promising in the genetic diagnosis of hearing loss.
[Mh] Termos MeSH primário: Surdez/genética
Doenças Genéticas Ligadas ao Cromossomo X/genética
Perda Auditiva Neurossensorial/genética
Proteínas Musculares/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Criança
Códon sem Sentido
Feminino
Mutação da Fase de Leitura
Genótipo
Seres Humanos
Masculino
Meia-Idade
Linhagem
Processamento de RNA
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (Muscle Proteins); 0 (SMPX protein, human)
[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:171231
[St] Status:MEDLINE


  2 / 15039 MEDLINE  
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[PMID]:29434199
[Au] Autor:Hayashi T; Ozaki H; Sasagawa Y; Umeda M; Danno H; Nikaido I
[Ad] Endereço:Bioinformatics Research Unit, Advanced Center for Computing and Communication, RIKEN, 2-1 Hirosawa Wako, Saitama, 351-0198, Japan.
[Ti] Título:Single-cell full-length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs.
[So] Source:Nat Commun;9(1):619, 2018 02 12.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Total RNA sequencing has been used to reveal poly(A) and non-poly(A) RNA expression, RNA processing and enhancer activity. To date, no method for full-length total RNA sequencing of single cells has been developed despite the potential of this technology for single-cell biology. Here we describe random displacement amplification sequencing (RamDA-seq), the first full-length total RNA-sequencing method for single cells. Compared with other methods, RamDA-seq shows high sensitivity to non-poly(A) RNA and near-complete full-length transcript coverage. Using RamDA-seq with differentiation time course samples of mouse embryonic stem cells, we reveal hundreds of dynamically regulated non-poly(A) transcripts, including histone transcripts and long noncoding RNA Neat1. Moreover, RamDA-seq profiles recursive splicing in >300-kb introns. RamDA-seq also detects enhancer RNAs and their cell type-specific activity in single cells. Taken together, we demonstrate that RamDA-seq could help investigate the dynamics of gene expression, RNA-processing events and transcriptional regulation in single cells.
[Mh] Termos MeSH primário: Sequenciamento de Nucleotídeos em Larga Escala/métodos
Células-Tronco Embrionárias Murinas/metabolismo
Processamento de RNA
RNA Longo não Codificante/genética
RNA Mensageiro/genética
Análise de Célula Única/métodos
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Diferenciação Celular
Elementos Facilitadores Genéticos
Éxons
Histonas/genética
Histonas/metabolismo
Íntrons
Camundongos
Células-Tronco Embrionárias Murinas/citologia
RNA Longo não Codificante/metabolismo
RNA Mensageiro/metabolismo
Análise de Sequência de RNA
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Histones); 0 (NEAT1 long non-coding RNA, mouse); 0 (RNA, Long Noncoding); 0 (RNA, Messenger)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180214
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-02866-0


  3 / 15039 MEDLINE  
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[PMID]:28460439
[Au] Autor:Pant V; Larsson CA; Aryal N; Xiong S; You MJ; Quintas-Cardama A; Lozano G
[Ad] Endereço:Department of Genetics, M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.
[Ti] Título:Tumorigenesis promotes Mdm4-S overexpression.
[So] Source:Oncotarget;8(16):25837-25847, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disruption of the p53 tumor suppressor pathway is a primary cause of tumorigenesis. In addition to mutation of the p53 gene itself, overexpression of major negative regulators of p53, MDM2 and MDM4, also act as drivers for tumor development. Recent studies suggest that expression of splice variants of Mdm2 and Mdm4 may be similarly involved in tumor development. In particular, multiple studies show that expression of a splice variant of MDM4, MDM4-S correlates with tumor aggressiveness and can be used as a prognostic marker in different tumor types. However, in the absence of prospective studies, it is not clear whether expression of MDM4-S in itself is oncogenic or is simply an outcome of tumorigenesis. Here we have examined the role of Mdm4-S in tumor development in a transgenic mouse model. Our results suggest that splicing of Mdm4 does not promote tumor development and does not cooperate with other oncogenic insults to alter tumor latency or aggressiveness. We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/genética
Expressão Gênica
Proteínas Nucleares/genética
Proteínas Proto-Oncogênicas/genética
[Mh] Termos MeSH secundário: Idoso
Animais
Biomarcadores
Linhagem Celular Tumoral
Aberrações Cromossômicas
Modelos Animais de Doenças
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Masculino
Camundongos
Camundongos Transgênicos
Meia-Idade
Mutação
Polimorfismo de Nucleotídeo Único
Processamento de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (MDM4 protein, human); 0 (Nuclear Proteins); 0 (Proto-Oncogene Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15552


  4 / 15039 MEDLINE  
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[PMID]:28470789
[Au] Autor:Kulkarni SS; Vasantha K; Gogri H; Parchure D; Madkaikar M; Férec C; Fichou Y
[Ad] Endereço:National Institute of Immunohaematology, Indian Council of Medical Research (NIIH-ICMR), Mumbai, India.
[Ti] Título:First report of Rh individuals in the Indian population and characterization of the underlying molecular mechanisms.
[So] Source:Transfusion;57(8):1944-1948, 2017 08.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Rh phenotype is an extremely rare condition characterized by no expression of Rh antigens at the surface of red blood cells. Although rare, genetic bases of this phenotype are well known and include mutations within either the RH (RHD and RHCE) genes or the RHAG gene. So far Rh has been reported in individuals of Caucasian, African, and Asian origin. Here, we report individuals from two families of Indian origin representing such a rare phenotype. STUDY DESIGN AND METHODS: Serologic analysis was carried out by testing with anti-D, -C, -c, -E, and -e in Rh individuals and their family members. RH genes were analyzed by standard molecular approaches, including Sanger sequencing and quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments. RHAG gene was investigated by exon-specific PCR amplification and Sanger sequencing. RESULTS: In one family, RHAG gene was found to be deleted at the homozygous state in the propositus, suggesting Rh of the regulator type. In the other family, a novel splice site variant in RHCE in cis with whole RHD gene deletion was identified at the homozygous state. Further functional analysis by minigene splicing assay showed that this variation, that is, c.801 + 1G>A, completely impairs normal splicing, then inactivating the expression of RhCE protein. Contrary to the former case, these data suggest Rh of the amorph type. CONCLUSION: Overall, we report for the first time the molecular mechanisms responsible for Rh phenotype in individuals of Indian origin. This study contributes to extend the molecular spectrum of variations in Rh individuals.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Linhagem
Sistema do Grupo Sanguíneo Rh-Hr/genética
[Mh] Termos MeSH secundário: Proteínas Sanguíneas/genética
Família
Feminino
Deleção de Genes
Seres Humanos
Índia/epidemiologia
Masculino
Glicoproteínas de Membrana/genética
Processamento de RNA/genética
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins); 0 (Membrane Glycoproteins); 0 (RHAG protein, human); 0 (RHCE protein, human); 0 (Rh-Hr Blood-Group System)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14150


  5 / 15039 MEDLINE  
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[PMID]:29236709
[Au] Autor:Barrett SP; Parker KR; Horn C; Mata M; Salzman J
[Ad] Endereço:Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States of America.
[Ti] Título:ciRS-7 exonic sequence is embedded in a long non-coding RNA locus.
[So] Source:PLoS Genet;13(12):e1007114, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ciRS-7 is an intensely studied, highly expressed and conserved circRNA. Essentially nothing is known about its biogenesis, including the location of its promoter. A prevailing assumption has been that ciRS-7 is an exceptional circRNA because it is transcribed from a locus lacking any mature linear RNA transcripts of the same sense. To study the biogenesis of ciRS-7, we developed an algorithm to define its promoter and predicted that the human ciRS-7 promoter coincides with that of the long non-coding RNA, LINC00632. We validated this prediction using multiple orthogonal experimental assays. We also used computational approaches and experimental validation to establish that ciRS-7 exonic sequence is embedded in linear transcripts that are flanked by cryptic exons in both human and mouse. Together, this experimental and computational evidence generates a new model for regulation of this locus: (a) ciRS-7 is like other circRNAs, as it is spliced into linear transcripts; (b) expression of ciRS-7 is primarily determined by the chromatin state of LINC00632 promoters; (c) transcription and splicing factors sufficient for ciRS-7 biogenesis are expressed in cells that lack detectable ciRS-7 expression. These findings have significant implications for the study of the regulation and function of ciRS-7, and the analytic framework we developed to jointly analyze RNA-seq and ChIP-seq data reveal the potential for genome-wide discovery of important biological regulation missed in current reference annotations.
[Mh] Termos MeSH primário: RNA/biossíntese
RNA/genética
[Mh] Termos MeSH secundário: Algoritmos
Processamento Alternativo
Animais
Química Encefálica
Éxons
Feminino
Células HEK293
Seres Humanos
Camundongos
Gravidez
Processamento de RNA
RNA Longo não Codificante/genética
Análise de Sequência de RNA/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (RNA, Long Noncoding); 0 (RNA, circular); 63231-63-0 (RNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007114


  6 / 15039 MEDLINE  
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[PMID]:28460014
[Au] Autor:Wu X; Wang SH; Sun J; Krainer AR; Hua Y; Prior TW
[Ad] Endereço:Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
[Ti] Título:A-44G transition in SMN2 intron 6 protects patients with spinal muscular atrophy.
[So] Source:Hum Mol Genet;26(14):2768-2780, 2017 07 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Spinal muscular atrophy (SMA) is a neuromuscular disease caused by reduced expression of survival of motor neuron (SMN), a protein expressed in humans by two paralogous genes, SMN1 and SMN2. These genes are nearly identical, except for 10 single-nucleotide differences and a 5-nucleotide insertion in SMN2. SMA is subdivided into four main types, with type I being the most severe. SMN2 copy number is a key positive modifier of the disease, but it is not always inversely correlated with clinical severity. We previously reported the c.859G > C variant in SMN2 exon 7 as a positive modifier in several patients. We have now identified A-44G as an additional positive disease modifier, present in a group of patients carrying 3 SMN2 copies but displaying milder clinical phenotypes than other patients with the same SMN2 copy number. One of the three SMN2 copies appears to have been converted from SMN1, but except for the C6T transition, no other changes were detected. Analyzed with minigenes, SMN1C6T displayed a ∼20% increase in exon 7 inclusion, compared to SMN2. Through systematic mutagenesis, we found that the improvement in exon 7 splicing is mainly attributable to the A-44G transition in intron 6. Using RNA-affinity chromatography and mass spectrometry, we further uncovered binding of the RNA-binding protein HuR to the -44 region, where it acts as a splicing repressor. The A-44G change markedly decreases the binding affinity of HuR, resulting in a moderate increase in exon 7 inclusion.
[Mh] Termos MeSH primário: Atrofia Muscular Espinal/genética
[Mh] Termos MeSH secundário: Animais
Células COS
Cercopithecus aethiops
Proteína Semelhante a ELAV 1/metabolismo
Éxons
Células HEK293
Células HeLa
Seres Humanos
Íntrons
Atrofia Muscular Espinal/metabolismo
Ligação Proteica
RNA/genética
Motivo de Reconhecimento de RNA
Processamento de RNA
Proteína 1 de Sobrevivência do Neurônio Motor/genética
Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo
Proteína 2 de Sobrevivência do Neurônio Motor/genética
Proteína 2 de Sobrevivência do Neurônio Motor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (ELAV-Like Protein 1); 0 (ELAVL1 protein, human); 0 (SMN1 protein, human); 0 (SMN2 protein, human); 0 (Survival of Motor Neuron 1 Protein); 0 (Survival of Motor Neuron 2 Protein); 63231-63-0 (RNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180225
[Lr] Data última revisão:
180225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx166


  7 / 15039 MEDLINE  
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[PMID]:29366779
[Au] Autor:Fukumura K; Inoue K; Mayeda A
[Ad] Endereço:Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake 470-1192, Aichi, Japan.
[Ti] Título:Splicing activator RNPS1 suppresses errors in pre-mRNA splicing: A key factor for mRNA quality control.
[So] Source:Biochem Biophys Res Commun;496(3):921-926, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human RNPS1 protein was first identified as a pre-mRNA splicing activator in vitro and RNPS1 regulates alternative splicing in cellulo. RNPS1 was also known as a peripheral factor of the exon junction complex (EJC). Here we show that cellular knockdown of RNPS1 induced a reduction of the wild-type aurora kinase B (AURKB) protein due to the induced aberrant pre-mRNA splicing events, indicating that the fidelity of AURKB pre-mRNA splicing was reduced. The major aberrant AURKB mRNA was derived from the upstream pseudo 5' and 3' splice sites in intron 5, which resulted in the production of the non-functional truncated AURKB protein. AURKB, is an essential mitotic factor, whose absence is known to cause multiple nuclei, and this multinucleation phenotype was recapitulated in RNPS1-knockdown cells. Importantly this RNPS1-knockdown phenotype was rescued by ectopic expression of AURKB, implying it is a major functional target of RNPS1. We found RNPS1 protein, not as a component of the EJC, binds directly to a specific element in the AURKB exon upstream of the authentic 5' splice site, and this binding is required for normal splicing. RNPS1-knockdown induces a parallel aberrant splicing pattern in a fully distinct pre-mRNA, MDM2, suggesting that RNPS1 is a global guardian of splicing fidelity. We conclude that RNPS1 is a key factor for the quality control of mRNAs that is essential for the phenotypes including cell division.
[Mh] Termos MeSH primário: Aurora Quinase B/genética
Genes Supressores
Precursores de RNA/genética
Processamento de RNA/genética
RNA Mensageiro/genética
Ribonucleoproteínas/genética
[Mh] Termos MeSH secundário: Células HeLa
Seres Humanos
Controle de Qualidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA Precursors); 0 (RNA, Messenger); 0 (RNPS1 protein, human); 0 (Ribonucleoproteins); EC 2.7.11.1 (AURKB protein, human); EC 2.7.11.1 (Aurora Kinase B)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE


  8 / 15039 MEDLINE  
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[PMID]:29178646
[Au] Autor:Konersman CG; Freyermuth F; Winder TL; Lawlor MW; Lagier-Tourenne C; Patel SB
[Ad] Endereço:Department of Neurosciences, University of California San Diego, San Diego, California.
[Ti] Título:Novel autosomal dominant TNNT1 mutation causing nemaline myopathy.
[So] Source:Mol Genet Genomic Med;5(6):678-691, 2017 11.
[Is] ISSN:2324-9269
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nemaline myopathy (NEM) is one of the three major forms of congenital myopathy and is characterized by diffuse muscle weakness, hypotonia, respiratory insufficiency, and the presence of nemaline rod structures on muscle biopsy. Mutations in troponin T1 (TNNT1) is 1 of 10 genes known to cause NEM. To date, only homozygous nonsense mutations or compound heterozygous truncating or internal deletion mutations in TNNT1 gene have been identified in NEM. This extended family is of historical importance as some members were reported in the 1960s as initial evidence that NEM is a hereditary disorder. METHODS: Proband and extended family underwent Sanger sequencing for TNNT1. We performed RT-PCR and immunoblot on muscle to assess TNNT1 RNA expression and protein levels in proband and father. RESULTS: We report a novel heterozygous missense mutation of TNNT1 c.311A>T (p.E104V) that segregated in an autosomal dominant fashion in a large family residing in the United States. Extensive sequencing of the other known genes for NEM failed to identify any other mutant alleles. Muscle biopsies revealed a characteristic pattern of nemaline rods and severe myofiber hypotrophy that was almost entirely restricted to the type 1 fiber population. CONCLUSION: This novel mutation alters a residue that is highly conserved among vertebrates. This report highlights not only a family with autosomal dominant inheritance of NEM, but that this novel mutation likely acts via a dominant negative mechanism.
[Mh] Termos MeSH primário: Miopatias da Nemalina/genética
Troponina T/genética
[Mh] Termos MeSH secundário: Adolescente
Sequência de Aminoácidos
Sequência de Bases
Homozigoto
Seres Humanos
Masculino
Músculo Esquelético/metabolismo
Músculo Esquelético/patologia
Mutação de Sentido Incorreto
Miopatias da Nemalina/diagnóstico
Linhagem
Polimorfismo de Nucleotídeo Único
RNA/química
RNA/isolamento & purificação
RNA/metabolismo
Processamento de RNA
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Alinhamento de Sequência
Análise de Sequência de DNA
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Troponin T); 63231-63-0 (RNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1002/mgg3.325


  9 / 15039 MEDLINE  
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[PMID]:29338026
[Au] Autor:Vanzyl EJ; Rick KRC; Blackmore AB; MacFarlane EM; McKay BC
[Ad] Endereço:Department of Biology, Carleton University, Ottawa ON, Canada.
[Ti] Título:Flow cytometric analysis identifies changes in S and M phases as novel cell cycle alterations induced by the splicing inhibitor isoginkgetin.
[So] Source:PLoS One;13(1):e0191178, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The spliceosome is a large ribonucleoprotein complex that catalyzes the removal of introns from RNA polymerase II-transcribed RNAs. Spliceosome assembly occurs in a stepwise manner through specific intermediates referred to as pre-spliceosome complexes E, A, B, B* and C. It has been reported that small molecule inhibitors of the spliceosome that target the SF3B1 protein component of complex A lead to the accumulation of cells in the G1 and G2/M phases of the cell cycle. Here we performed a comprehensive flow cytometry analysis of the effects of isoginkgetin (IGG), a natural compound that interferes with spliceosome assembly at a later step, complex B formation. We found that IGG slowed cell cycle progression in multiple phases of the cell cycle (G1, S and G2) but not M phase. This pattern was somewhat similar to but distinguishable from changes associated with an SF3B1 inhibitor, pladienolide B (PB). Both drugs led to a significant decrease in nascent DNA synthesis in S phase, indicative of an S phase arrest. However, IGG led to a much more prominent S phase arrest than PB while PB exhibited a more pronounced G1 arrest that decreased the proportion of cells in S phase as well. We also found that both drugs led to a comparable decrease in the proportion of cells in M phase. This work indicates that spliceosome inhibitors affect multiple phases of the cell cycle and that some of these effects vary in an agent-specific manner despite the fact that they target splicing at similar stages of spliceosome assembly.
[Mh] Termos MeSH primário: Biflavonoides/farmacologia
Divisão Celular/efeitos dos fármacos
Processamento de RNA/efeitos dos fármacos
Fase S/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ciclo Celular/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Compostos de Epóxi/farmacologia
Citometria de Fluxo
Células HCT116
Seres Humanos
Macrolídeos/farmacologia
Precursores de RNA/metabolismo
Spliceossomos/efeitos dos fármacos
Spliceossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biflavonoids); 0 (Epoxy Compounds); 0 (Macrolides); 0 (RNA Precursors); 0 (isoginkgetin); 0 (pladienolide B)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191178


  10 / 15039 MEDLINE  
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[PMID]:28467899
[Au] Autor:Rot G; Wang Z; Huppertz I; Modic M; Lence T; Hallegger M; Haberman N; Curk T; von Mering C; Ule J
[Ad] Endereço:Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, Winterthurerstrasse 190, 8057 Zurich, Switzerland; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: gregor.rot@uzh.ch.
[Ti] Título:High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43.
[So] Source:Cell Rep;19(5):1056-1067, 2017 May 02.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many RNA-binding proteins (RBPs) regulate both alternative exons and poly(A) site selection. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of iCLIP and RNA motif analyses with RNA-seq and 3' mRNA sequencing. This reveals at nucleotide resolution the "RNA maps" describing how the RNA binding positions of RBPs relate to their regulatory functions. We use this approach to examine how TDP-43, an RBP involved in several neurodegenerative diseases, binds around its regulated poly(A) sites. Binding close to the poly(A) site generally represses, whereas binding further downstream enhances use of the site, which is similar to TDP-43 binding around regulated exons. Our RNAmotifs2 software also identifies sequence motifs that cluster together with the binding motifs of TDP-43. We conclude that TDP-43 directly regulates diverse types of pre-mRNA processing according to common position-dependent principles.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/metabolismo
Poliadenilação
Processamento de RNA
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
Ligação Proteica
Sinais de Poliadenilação na Ponta 3' do RNA
RNA Mensageiro/química
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (RNA, Messenger); 0 (TDP-43 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE



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