Adenylyl Cyclase Plays a Regulatory Role in Development, Stress Resistance and Secondary Metabolism in Fusarium fujikuroi

The ascomycete fungus Fusarium fujikuroi (Gibberella fujikuroi MP-C) produces secondary metabolites of biotechnological interest, such as gibberellins, bikaverin, and carotenoids. Production of these metabolites is regulated by nitrogen availability and, in a specific manner, by other environmental signals, such as light in the case of the carotenoid pathway. A complex regulatory network controlling these processes is recently emerging from the alterations of metabolite production found through the mutation of different regulatory genes. Here we show the effect of the targeted mutation of the acyA gene of F. fujikuroi, coding for adenylyl cyclase. Mutants lacking the catalytic domain of the AcyA protein showed different phenotypic alterations, including reduced growth, enhanced production of unidentified red pigments, reduced production of gibberellins and partially derepressed carotenoid biosynthesis in the dark. The phenotype differs in some aspects from that of similar mutants of the close relatives F. proliferatum and F. verticillioides: contrary to what was observed in these species, ΔacyA mutants of F. fujikuroi showed enhanced sensitivity to oxidative stress (H2O2), but no change in heavy metal resistance or in the ability to colonize tomato tissue, indicating a high versatility in the regulatory roles played by cAMP in this fungal group

EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination

The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation

EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination

et al.The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation.This work was supported by Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation, MICINN) (grant numbers SAF2008-03147 and SAF2011_24225 to LdelP and SAF-2010-19256 to BJ); by Comunidad Autónoma de Madrid (grant numbers S2010/BMD-2542 to LdelP), by the 7th Research Framework Programme of the European Union (grant number METOXIA project ref. HEALTH-F2-2009-222741 to LdelP); by CSIC (JAE DOC 2010/FSE2007-2013 to OR) and by Fondo de Investigación Sanitaria/Instituto de Salud Carlos III (grants PI08/90856 and PS09/00227 to LS).Peer Reviewe

HPLC Analysis of Carotenoids in Neurosporaxanthin-Producing Fungi

13 Páginas; 4 FigurasThe ascomycetous fungi Fusarium fujikuroi and Neurospora crassa are widely used as research models in the study of secondary metabolism and photobiology, respectively. Both fungi exhibit a similar carotenoid pathway, for which all the genes and enzymes have been identified. Under standard laboratory conditions, either F. fujikuroi or N. crassa accumulate a mixture of neurosporaxanthin, a carboxylic apocarotenoid acid, and several of its carotene precursors. We formerly described methods for the identification and quantification of neurosporaxanthin. However, the differences in polarity between this acidic xanthophyll and neutral carotenes make their global analysis cumbersome. Here we propose a simple HPLC methodology for the efficient separation of neurosporaxanthin and earlier pathway intermediates in a single HPLC run. This method should be useful to check the abundance of neurosporaxanthin under different experimental conditions and to evaluate the relative proportions of their different carotene precursors. To assess the validity of the method, we have compared the carotenoid profiles in samples of mycelia of F. fujikuroi and conidia of N. crassa, in both cases obtained from surface cultures of a wild strain of each species.We thank the Spanish Government (projects BIO2012-39716, BIO2015-69613-R, AGL2014-53195R, and CaRed Network BIO2015-71703-REDT) and Junta de Andalucía (project CTS-6638) for financial support.Peer reviewe

Vilano : programa integrador de educación ambiental

El trabajo obtuvo el Segundo Premio de la Modalidad B de los 'Premios Tomás García Verdejo' a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso académico 2013/2014Se describe el proyecto llevado a cabo en el IES Tamujal (Arroyo de San Serván, Badajoz) que tenía como eje central el campo de la educación ambiental. Algunas de las actividades llevadas a cabo fueron: la creación de un gabinete de curiosidades de los objetos que se encuentran en la naturaleza, elaboración de un herbario de enseñanza, desarrollo del jardín botánico del centro, un taller de botánica y un huerto escolarExtremaduraES