Human prefoldin modulates co-transcriptional pre-mRNA splicing

Trabajo presentado en el IV Meeting RNALife, celebrado en Sevilla (España) del 12 al 13 de julio de 2021.Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a co-chaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing

Human prefoldin modulates co-transcriptional pre-mRNA splicing.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P to S.C. and BFU2017-85420-R to J.C.R.] co-financed with European Union funds (FEDER); Andalusian Government [P12-BIO1938MO, BIO271, US-1256285 to S.C., BIO321 to J.C.R.]; Junta de Andalucía (to L.P.-B.). Funding for open access charge: Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P]

Utilización de funciones de transferencia para simular los procesos hídricos que intervienen en las reservas naturales de las lagunas Amarga y Dulce (Córdoba)

On the base of the equation of water balance some empirical functions have been adjusted to simulate the processes of water transfer between the elements that can intervene into water dynamics of wetlands. In this article the used methodology has been described and also the results of the application for two lagoons: "Amarga" and "Dulce", both came from South of Córdoba, are showed. In the simulation of the water functioning other processes have been included like for example drainage of "Dulce" lagoon by means of the construction of drains towards "Amarga" lagoon or like for example the natural opening by hydraulic overcharge. The large period of simulation has allowed to obtain statistically representative values of some interesting variables for the management of the lagoons such averages, ranges and percentage distribution of the flooded surface and stored volume. Also it has been possible to simulate the new water situation after the recent elimination of the drainage of "Dulce" lagoon towards "Amarga" lagoon. This communication gathers a part of the taken works carried out by "Consejería de Medio Ambiente de la Junta de Andalucía" in the "Estudio hidrogeológico de las lagunas del Sur de Córdoba: Lagunas del Rincón y Santiago, Lagunas Amarga y Dulce (NET 291875/1)" inside the general Project "Life-Naturaleza conservación de Humedales Andaluces (LIFE NAT 03/E000055)".Sobre la base de la ecuación del balance hídrico se han ajustado unas funciones empíricas para simular los procesos de transferencia de agua entre los distintos elementos que pueden intervenir en la dinámica hídrica de los humedales. En este artículo se describe la metodología empleada y se recogen los resultados de su aplicación a las lagunas Amarga y Dulce del Sur de Córdoba. En la simulación del funcionamiento hídrico se han incluido otros procesos tales como la desecación de la laguna Dulce mediante la construcción de drenes hacia la laguna Amarga o la apertura natural de sumideros debido a la sobrecarga hidráulica. El largo periodo de simulación realizado ha permitido obterner valores estadísticamente representativos de algunas variables interesantes para la gestión de las lagunas, tales como medias, rangos y distribución porcentual de la superficie inundada y del volumen almacenado. También se ha podido simular la nueva situación hídrica generada tras la reciente eliminación del drenaje de la laguna Dulce hacia la laguna Amarga. Esta comunicación recoge una parte de los trabajos llevados a cabo por la Consejería de Medio Ambiente de la Junta de Andalucía en el Estudio hidrogeológico de las lagunas del Sur de Córdoba: Lagunas del Rincón y Santiago, Lagunas Amargas y Dulce (NET 291875/1) dentro del proyecto general Life-Naturaleza conservación de Humedales Andaluces (LIFE NAT 03/ E000055)

Human prefoldin modulates co-transcriptional pre-mRNA splicing

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.Ministerio de Ciencia e Innovación BFU2016-77728-C3-1-P, BFU2017-85420-RJunta de Andalucía P12- BIO1938MO, BIO271, US-1256285, BIO32

Powering of an HTS dipole insert-magnet operated standalone in helium gas between 5 and 85 K

International audienceThis paper describes the standalone magnet cold testing of the high temperature superconducting (HTS) magnet Feather-M2.1-2. This magnet was constructed within the European funded FP7-EUCARD2 collaboration to test a Roebel type HTS cable, and is one of the first high temperature superconducting dipole magnets in the world. The magnet was operated in forced flow helium gas with temperatures ranging between 5 and 85 K. During the tests a magnetic dipole field of 3.1 T was reached inside the aperture at a current of 6.5 kA and a temperature of 5.7 K. These values are in agreement with the self-field critical current of the used SuperOx cable assembled with Sunam tapes (low-performance batch), thereby confirming that no degradation occurred during winding, impregnation, assembly and cool-down of the magnet. The magnet was quenched many tens of times by ramping over the critical current and no degradation nor training was evident. During the tests the voltage over the coil was monitored in the microvolt range. An inductive cancellation wire was used to remove the inductive component, thereby significantly reducing noise levels. Close to the quench current, drift was detected both in temperature and voltage over the coil. This drifting happens in a time scale of minutes and is a clear indication that the magnet has reached its limit. All quenches happened approximately at the same average electric field and thus none of the quenches occurred unexpectedly