Genetic and genomic analysis of RNA polymerase II backtracking in saccharomyces cerevisiae

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Factores de riesgos presentes y su relación con los accidentes laborales en trabajadores del Hospital "Bertha Calderón Roque". Managua, Enero - Junio 2004.

Tiene por objetivo identificar los factores de riesgo presentes y su relación con los accidentes laborales en trabajadores del hospital Bertha Calderón Roque

TFIIS is required for the balanced expression of the genes encoding ribosomal components under transcriptional stress

Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation. Yeast cells do not require TFIIS for viability, unless they suffer severe transcriptional stress due to NTP-depleting drugs like 6-azauracil or mycophenolic acid. In order to broaden our knowledge on the role of TFIIS under transcriptional stress, we carried out a genetic screening for suppressors of TFIIS-lacking cells’ sensitivity to 6-azauracil and mycophenolic acid. Five suppressors were identified, four of which were related to the transcriptional regulation of those genes encoding ribosomal components [rRNAs and ribosomal proteins (RP)], including global regulator SFP1. This led us to discover that RNA polymerase II is hypersensitive to the absence of TFIIS under NTP scarcity conditions when transcribing RP genes. The absence of Sfp1 led to a profound alteration of the transcriptional response to NTP-depletion, thus allowing the expression of RP genes to resist these stressful conditions in the absence of TFIIS. We discuss the effect of transcriptional stress on ribosome biogenesis and propose that TFIIS contributes to prevent a transcriptional imbalance between rDNA and RP genes.España Ministerio de Economía y competitividad BFU2007-67575-C03-02España Ministerio de Economía y competitividad BFU-2010-21975-C03-03Andalucía, Junta de Andalucía P07-CVI-02623Andalucía, Junta de Andalucía P08-CVI-035

The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4

Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its posttranscriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1-decaysome and Ccr4–Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome

One step back before moving forward: regulation of transcription elongation by arrest and backtracking

RNA polymerase II backtracking is a well-known phenomenon, but its involvement in gene regulation is yet to be addressed. Structural studies into the backtracked complex, new reactivation mechanisms and genome-wide approaches are shedding some light on this interesting aspect of gene transcription. In this review, we briefly summarise these new findings, comment about some results recently obtained in our laboratory, and propose a new model for the influence of the chromatin context on RNA polymerase II backtracking.Ministerio de Economía y Competitividad de España. BFU2007-67575-C03-02 y BFU-2010-21975-C03-03Junta de Andalucía. P07-CVI-02623 y P08-CVI-0350

Use of restoration plantings to enhance bird seed dispersal at the roadside: failures and prospects

Plantings are commonly used in roadside reclamation for ornamental purposes and for increasing slope stability and road safety. However, the role of these plantings in restoring ecological processes, such as seed dispersal, has received little attention. We carried out a study to assess the potential role of plantings on roadside embankments to attract frugivorous birds and to enhance seed dispersal mediated by birds from the surrounding landscape. We examined: (1) bird species richness and abundance; (2) patterns of avian spatial distribution within embankments and (3) seed dispersal mediated by birds. Bird richness and abundance did not differ between embankments with and without plantings. However, birds were not distributed randomly within embankments, with levels of species richness and abundance for facultative frugivorous between 4.8–8 times higher in areas closer to plantings. An analysis of bird droppings showed that birds only dispersed seeds of the planted species since no seeds of woody plants from matrices were detected. These results suggest that plantings acted as selective bird attractors, providing food and perches for frugivorous species. Nevertheless, the scarcity of seed-dispersing birds in the surrounding agricultural landscape prevented plantings from enhancing seed dispersal and connectivity to adjacent habitat

Boron-doped diamond by 9 MeV microbeam implantation: Damage and recovery

Diamond properties can be tuned by doping and ion-beam irradiation is one of the most powerful techniques to do it in a controlled way, but it also produces damage and other aftereffects. Of particular interest is boron doping which, in moderate concentrations, causes diamond to become a p-type semiconductor and, at higher boron concentrations, a superconductor. Nevertheless, the preparation of superconducting boron-doped diamond by ion implantation is hampered by amorphization and subsequent graphitization after annealing. The aim of this work was to explore the possibility of creating boron-doped diamond superconducting regions and to provide a new perspective on the damage induced in diamond by MeV ion irradiation. Thus, a comprehensive analysis of the damage and eventual recovery of diamond when irradiated with 9 MeV B ions with different fluences has been carried out, combining Raman, photoluminescence, electrical resistivity, X-ray diffraction and Rutherford Backscattering/Ion-channeling. It is found that, as the B fluence increases, carbon migrates to interstitial sites outside of the implantation path and an amorphous fraction increases within the path. For low fluences (∼1015 ions/cm2), annealing at 1000 °C is capable to fully recovering the diamond structure without graphitization. However, for higher fluences (≥5 × 1016 ions/cm2), those required for superconductivity, the recovery is important, but some disorder still remains. For high fluences, annealing at 1200 °C is detrimental for the diamond lattice and graphite traces appear. The incomplete healing of the diamond lattice and the interstitial location of B can explain that optimally doped samples do not exhibit superconductivityThis work has been partially supported by the Ministerio de Ciencia e Innovacion ´ of Spain (Project grants PID2020-112770RB-C22/MCIN/ AEI/10.13039/501100011033, PID2021-127033OB-C21/MCIN/AEI/ 10.13039/501100011033, and PID2021-127498NB-I00/AEI/FEDER/ 10.13039/501100011033). We also acknowledge financial support from MCIN/AEI/10.13039/501100011033, through the “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000805- M), as well as from the Autonomous Community of Madrid through program S2018/NMT-4321 (NANOMAGCOST-CM

High drug resistance prevalence among vertically HIV-Infected patients transferred from pediatric care to adult units in Spain

BACKGROUND: Antiretroviral treatment (ART) has contributed to increased life expectancy of HIV-1 infected children. In developed countries, an increasing number of children reaching adulthood are transferred to adult units. The objectives were to describe the demographic and clinical features, ART history, antiviral drug resistance and drug susceptibility in HIV-1 perinatally infected adolescents transferred to adult care units in Spain from the Madrid Cohort of HIV-1 infected children. METHODS: Clinical, virological and immunological features of HIV-1 vertically infected patients in the Madrid Cohort of HIV-infected children were analyzed at the time of transfer. Pol sequences from each patient were recovered before transfer. Resistance mutations according to the InternationaI AIDS Society 2011 list were identified and interpreted using the Stanford algorithm. Results were compared to the non-transferred HIV-1 infected pediatric cohort from Madrid. RESULTS: One hundred twelve infected patients were transferred to adult units between 1997 and 2011. They were mainly perinatally infected (93.7%), with a mean nadir CD4+-T-cells count of 10% and presented moderate or severe clinical symptoms (75%). By the time of transfer, the mean age was 18.9 years, the mean CD4+T-cells count was 627.5 cells/ml, 64.2% presented more than 350 CD4+T-cells/ml and 47.3% had ≤200 RNA-copies/ml. Most (97.3%) were ART experienced receiving Highly Active ART (HAART) (84.8%). Resistance prevalence among pretreated was 50.9%, 76.9% and 36.5% for Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-NRTI (NNRTI), respectively. Resistance mutations were significantly higher among transferred patients compared to non-transferred for the PI+NRTI combination (19% vs. 8.4%). Triple resistance was similar to non-transferred pediatric patients (17.3% vs. 17.6%). CONCLUSION: Despite a good immunological and virological control before transfer, we found high levels of resistance to PI, NRTI and triple drug resistance in HIV-1 infected adolescents transferred to adult units