RESUMO
Gene expression involving RNA polymerase II is regulated by the concerted interplay between mRNA synthesis and degradation, crosstalk in which mRNA decay machinery and transcription machinery respectively impact transcription and mRNA stability. Rpb4, and likely dimer Rpb4/7, seem the central components of the RNA pol II governing these processes. In this work we unravel the molecular mechanisms participated by Rpb4 that mediate the posttranscriptional events regulating mRNA imprinting and stability. By RIP-Seq, we analysed genome-wide the association of Rpb4 with mRNAs and demonstrated that it targeted a large population of more than 1400 transcripts. A group of these mRNAs was also the target of the RNA binding protein, Puf3. We demonstrated that Rpb4 and Puf3 physically, genetically, and functionally interact and also affect mRNA stability, and likely the imprinting, of a common group of mRNAs. Furthermore, the Rpb4 and Puf3 association with mRNAs depends on one another. We also demonstrated, for the first time, that Puf3 associates with chromatin in an Rpb4-dependent manner. Our data also suggest that Rpb4 could be a key element of the RNA pol II that coordinates mRNA synthesis, imprinting and stability in cooperation with RBPs.
Assuntos
Impressão Genômica , RNA Polimerase II/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Sítios de Ligação , Cromatina/química , Cromatina/metabolismo , Regulação Fúngica da Expressão Gênica , Anotação de Sequência Molecular , Ligação Proteica , RNA Polimerase II/metabolismo , Estabilidade de RNA , RNA Mensageiro/classificação , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Transcrição GênicaRESUMO
Rabbit hemorrhagic disease (RHD) is a highly infectious disease in European rabbits (Oryctolagus cuniculus), caused by a virus belonging to the genus Lagovirus (RHDV; family Caliciviridae). In 2010, a new genotype of RHDV (RHDV2 or RHDVb, currently designated GI.2) emerged in France, affecting both domestic rabbits, even those vaccinated for the classical RHDV genotypes (currently designated GI.1) and wild rabbits. GI.2 was subsequently identified in other European countries. The aim of the present study was to monitor the GI.2 epidemic in wild rabbits in Andalusia (southern Spain) during the period 2013-2017. At the beginning of summer 2013, high mortalities were detected in wild rabbit populations in southern Spain. A total of 96 affected hunting or protected areas were surveyed. The first outbreak was observed on June 2013. The number of outbreaks sharply increased in 2013 and 2014, with a decreasing trend being observed during the following years. The spatial distribution of GI.2 was not homogeneous, since most of the detected outbreaks were concentrated in the western part of Andalusia. The outbreaks peaked in winter and spring and have been detected in the last five consecutive years, which suggests endemic circulation of GI.2 in wild rabbit populations in Spain. A total of 190 dead rabbits from 87 of the 96 areas surveyed were collected during the study period. Mortality affected rabbits of different age classes, including kittens. RT-PCR confirmed the presence of GI.2 RNA in the livers of 185 of the 190 (97.4%) rabbits. Phylogenetic analysis performed on eleven samples collected in different provinces of Andalusia between 2013 and 2017, showed high nucleotide identity with GI.2 strains Spain, France and Portugal. The results constitute an important step in understanding of the emergence and spread of GI.2 in this country and will provide valuable information for the development of surveillance programs in Europe.
Assuntos
Animais Selvagens , Infecções por Caliciviridae/veterinária , Epidemias/veterinária , Vírus da Doença Hemorrágica de Coelhos , Coelhos/virologia , Animais , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Doenças Transmissíveis Emergentes/veterinária , Doenças Transmissíveis Emergentes/virologia , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Espanha/epidemiologiaRESUMO
Los casos de resistencia a poliquimioterapia en cáncer inflamatorio de mama representan un problema clínico difícil de resolver, sobre todo en pacientes jóvenes. Se presenta el caso de una paciente tratada por un cáncer de mama que presenta una recidiva local a los 4 años en forma de carcinoma inflamatorio, que resultó resistente a múltiples pautas quimioterápicas y que finalmente fue tratada mediante cirugía radical y reparación mediante colgajo de dorsal ancho(AU)
The cases of resistance to chemotherapy in inflammatory breast cancer represent a difficult clinical problem solving, especially in young patients. A case of a patient for breast cancer that has a local recurrence at 4 years in the form of inflammatory carcinoma, which were resistant to multiple chemotherapy regimens and eventually was treated by radical surgery and repair of latissimus dorsi flap(AU)
