HuR is exported to the cytoplasm in oral cancer cells in a different manner from that of normal cells

HuR, a ubiquitously expressed member of the Hu protein family that binds and stabilizes an AU-rich element (ARE)-containing mRNAs, is known to shuttle between the nucleus and the cytoplasm via several export pathways. When normal cells were treated with heat shock, HuR was exported to the cytoplasm in a chromosome maintenance region 1 (CRM1)-dependent manner. However, in this study, we demonstrate that HuR is exported to the cytoplasm in oral cancer cells even if the cells were treated with the inhibitor of the CRM1-independent export pathway. Immunohistochemical and biochemical analyses showed that HuR existed in both the cytoplasm and the nucleus in oral cancer cells, such as HSC-3 and Ca9.22, but existed entirely inside the nucleus in normal cells. AU-rich element-mRNAs were also exported to the cytoplasm and stabilised in the oral cancer cells, which were inhibited by HuR knockdown. This export of HuR was not affected by at least 7 h of treatment of leptomycin B (LMB), which is an inhibitor of the CRM1-dependent export pathway. These findings suggest that HuR is exported to the cytoplasm in oral carcinoma cells in a different manner from that of normal cells, and is likely to occur through the perturbation of a normal export pathway

Didáctica de la geometría: análisis de la enseñanza de la geometría a partir de un estudio de campo según el modelo de Van Hiele

El objetivo es la realización de la medida del grado de conocimiento de la geometría, dentro del marco teórico ofrecido por el modelo de van Hiele aplicado al sistema educativo español, que permitan estudiar la evolución de los conocimientos en geometría a lo largo de las etapas educativas de Enseñanza Primaria, Secundaria, Bachillerato y Universidad. Seleccionamos y homologamos el cuestionario de Usiskin para la medida del nivel de razonamiento de van Hiele, por ser el único que ha sido aplicado en los cinco continentes. De esta forma, las medidas de los niveles de razonamiento realizadas en este trabajo, son h omologables y comparables con las de otros investigadores que han trabajado en otras latitudes. El primer trabajo de campo que presentamos es la determinación de los niveles de razonamiento y las fases de aprendizaje de las actividades de geometría p ropuestas por libros de texto de Educación Primaria, Secundaria Obligatoria y Bachillerato. Así mostramos una radiografía objetiva de los niveles de razonamiento de van Hiele que el sistema educativo español propone para alcanzar por los alumnos. Ade más, son una referencia ineludible para compararlos con los niveles de razonamiento medidos en alumnos, que permite evaluar el grado en que se han conseguido los objetivos en el aprendizaje de la geometría. Realizamos la medición de los niveles de ra zonamiento en alumnos de las etapas: Educación Primaria, Secundaria, Bachillerato y Universitaria. Hemos aplicado 1120 cuestionarios a 934 alumnos de las citadas etapas. Aplicamos el cuestionario de Usiskin en cuatro centros de Enseñanza Media en Mad rid de titularidad pública, concertada y privada, así como a ocho grupos de las facultades de Educación de las UAM y UCM, así como a un grupo de mi asignatura Geometría Sagrada. Analizamos los resultados de la medida del nivel de razonamiento de van Hiele obtenido al aplicar el cuestionario de Usiskin a los alumnos de Educación Primaria, Secundaria, Bachillerato y Enseñanza Universitaria. Contrastamos los niveles de razonamiento medidos con los que obtuvimos al analizar los libros de texto de ge ometría, para estimar la eficacia del sistema educativo en el aprendizaje de la geometría. Se analizan sus implicaciones en la Enseñanza de la Geometría

Genomic origin and nuclear localization of TERRA telomeric repeat-containing RNA: from Darkness to Dawn.

Long noncoding RNAs, produced from distinct regions of the chromosomes, are emerging as new key players in several important biological processes. The long noncoding RNAs add a new layer of complexity to cellular regulatory pathways, from transcription to cellular trafficking or chromatin remodeling. More than 25 years ago, the discovery of a transcriptional activity at telomeres of protozoa ended the long-lasting belief that telomeres were transcriptionally silent. Since then, progressively accumulating evidences established that production of TElomeric Repeat-containing RNA (TERRA) was a general feature of eukaryotic cells. Whether TERRA molecules always originate from the telomeres or whether they can be transcribed from internal telomeric repeats as well is however still a matter of debate. Whether TERRA transcripts always localize to telomeres and play similar roles in all eukaryotic cells is also unclear. We review the studies on TERRA localization in the cell, its composition and some aspects of its transcriptional regulation to summarize the current knowledge and controversies about the genomic origin of TERRA, with a focus on human and mouse TERRA

Translational Control of TOP2A Influences Doxorubicin Efficacy▿

The cellular abundance of topoisomerase IIα (TOP2A) critically maintains DNA topology after replication and determines the efficacy of TOP2 inhibitors in chemotherapy. Here, we report that the RNA-binding protein HuR, commonly overexpressed in cancers, binds to the TOP2A 3′-untranslated region (3′UTR) and increases TOP2A translation. Reducing HuR levels triggered the recruitment of TOP2A transcripts to RNA-induced silencing complex (RISC) components and to cytoplasmic processing bodies. Using a novel MS2-tagged RNA precipitation method, we identified microRNA miR-548c-3p as a mediator of these effects and further uncovered that the interaction of miR-548c-3p with the TOP2A 3′UTR repressed TOP2A translation by antagonizing the action of HuR. Lowering TOP2A by silencing HuR or by overexpressing miR-548c-3p selectively decreased DNA damage after treatment with the chemotherapeutic agent doxorubicin. In sum, HuR enhances TOP2A translation by competing with miR-548c-3p; their combined actions control TOP2A expression levels and determine the effectiveness of doxorubicin