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1.
RNA ; 24(9): 1255-1265, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29959282

RESUMEN

During terminal erythropoiesis, the splicing machinery in differentiating erythroblasts executes a robust intron retention (IR) program that impacts expression of hundreds of genes. We studied IR mechanisms in the SF3B1 splicing factor gene, which expresses ∼50% of its transcripts in late erythroblasts as a nuclear isoform that retains intron 4. RNA-seq analysis of nonsense-mediated decay (NMD)-inhibited cells revealed previously undescribed splice junctions, rare or not detected in normal cells, that connect constitutive exons 4 and 5 to highly conserved cryptic cassette exons within the intron. Minigene splicing reporter assays showed that these cassettes promote IR. Genome-wide analysis of splice junction reads demonstrated that cryptic noncoding cassettes are much more common in large (>1 kb) retained introns than they are in small retained introns or in nonretained introns. Functional assays showed that heterologous cassettes can promote retention of intron 4 in the SF3B1 splicing reporter. Although many of these cryptic exons were spliced inefficiently, they exhibited substantial binding of U2AF1 and U2AF2 adjacent to their splice acceptor sites. We propose that these exons function as decoys that engage the intron-terminal splice sites, thereby blocking cross-intron interactions required for excision. Developmental regulation of decoy function underlies a major component of the erythroblast IR program.


Asunto(s)
Empalme Alternativo , Eritroblastos/citología , Factores de Empalme de ARN/genética , Análisis de Secuencia de ARN/métodos , Diferenciación Celular , Células Cultivadas , Eritroblastos/química , Exones , Humanos , Intrones , Degradación de ARNm Mediada por Codón sin Sentido , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Sitios de Empalme de ARN , Factores de Empalme de ARN/metabolismo , Factor de Empalme U2AF/metabolismo
2.
Nature ; 512(7515): 393-9, 2014 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-24670639

RESUMEN

Animal transcriptomes are dynamic, with each cell type, tissue and organ system expressing an ensemble of transcript isoforms that give rise to substantial diversity. Here we have identified new genes, transcripts and proteins using poly(A)+ RNA sequencing from Drosophila melanogaster in cultured cell lines, dissected organ systems and under environmental perturbations. We found that a small set of mostly neural-specific genes has the potential to encode thousands of transcripts each through extensive alternative promoter usage and RNA splicing. The magnitudes of splicing changes are larger between tissues than between developmental stages, and most sex-specific splicing is gonad-specific. Gonads express hundreds of previously unknown coding and long non-coding RNAs (lncRNAs), some of which are antisense to protein-coding genes and produce short regulatory RNAs. Furthermore, previously identified pervasive intergenic transcription occurs primarily within newly identified introns. The fly transcriptome is substantially more complex than previously recognized, with this complexity arising from combinatorial usage of promoters, splice sites and polyadenylation sites.


Asunto(s)
Drosophila melanogaster/genética , Perfilación de la Expresión Génica , Transcriptoma/genética , Empalme Alternativo/genética , Animales , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/citología , Femenino , Masculino , Anotación de Secuencia Molecular , Tejido Nervioso/metabolismo , Especificidad de Órganos , Poli A/genética , Poliadenilación , Regiones Promotoras Genéticas/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Caracteres Sexuales , Estrés Fisiológico/genética
3.
Nature ; 494(7437): 341-4, 2013 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-23389447

RESUMEN

The release of carbon from tropical forests may exacerbate future climate change, but the magnitude of the effect in climate models remains uncertain. Coupled climate-carbon-cycle models generally agree that carbon storage on land will increase as a result of the simultaneous enhancement of plant photosynthesis and water use efficiency under higher atmospheric CO(2) concentrations, but will decrease owing to higher soil and plant respiration rates associated with warming temperatures. At present, the balance between these effects varies markedly among coupled climate-carbon-cycle models, leading to a range of 330 gigatonnes in the projected change in the amount of carbon stored on tropical land by 2100. Explanations for this large uncertainty include differences in the predicted change in rainfall in Amazonia and variations in the responses of alternative vegetation models to warming. Here we identify an emergent linear relationship, across an ensemble of models, between the sensitivity of tropical land carbon storage to warming and the sensitivity of the annual growth rate of atmospheric CO(2) to tropical temperature anomalies. Combined with contemporary observations of atmospheric CO(2) concentration and tropical temperature, this relationship provides a tight constraint on the sensitivity of tropical land carbon to climate change. We estimate that over tropical land from latitude 30° north to 30° south, warming alone will release 53 ± 17 gigatonnes of carbon per kelvin. Compared with the unconstrained ensemble of climate-carbon-cycle projections, this indicates a much lower risk of Amazon forest dieback under CO(2)-induced climate change if CO(2) fertilization effects are as large as suggested by current models. Our study, however, also implies greater certainty that carbon will be lost from tropical land if warming arises from reductions in aerosols or increases in other greenhouse gases.


Asunto(s)
Ciclo del Carbono/fisiología , Dióxido de Carbono/metabolismo , Cambio Climático , Modelos Teóricos , Árboles/metabolismo , Clima Tropical , Dióxido de Carbono/análisis , Respiración de la Célula , Fotosíntesis , Lluvia , Temperatura , Incertidumbre
5.
Nature ; 484(7393): 228-32, 2012 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-22498628

RESUMEN

Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean. These links are extensive, influencing a range of climate processes such as hurricane activity and African Sahel and Amazonian droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures, but climate models have so far failed to reproduce these interactions and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.


Asunto(s)
Aerosoles , Clima , Calentamiento Global/estadística & datos numéricos , Océano Atlántico , Sequías , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Actividades Humanas , Radiación , Agua de Mar , Temperatura , Erupciones Volcánicas , Movimientos del Agua
6.
Glob Chang Biol ; 23(12): 5032-5044, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28449261

RESUMEN

The future of the Amazon rainforest is unknown due to uncertainties in projected climate change and the response of the forest to this change (forest resiliency). Here, we explore the effect of some uncertainties in climate and land surface processes on the future of the forest, using a perturbed physics ensemble of HadCM3C. This is the first time Amazon forest changes are presented using an ensemble exploring both land vegetation processes and physical climate feedbacks in a fully coupled modelling framework. Under three different emissions scenarios, we measure the change in the forest coverage by the end of the 21st century (the transient response) and make a novel adaptation to a previously used method known as "dry-season resilience" to predict the long-term committed response of the forest, should the state of the climate remain constant past 2100. Our analysis of this ensemble suggests that there will be a high chance of greater forest loss on longer timescales than is realized by 2100, especially for mid-range and low emissions scenarios. In both the transient and predicted committed responses, there is an increasing uncertainty in the outcome of the forest as the strength of the emissions scenarios increases. It is important to note however, that very few of the simulations produce future forest loss of the magnitude previously shown under the standard model configuration. We find that low optimum temperatures for photosynthesis and a high minimum leaf area index needed for the forest to compete for space appear to be precursors for dieback. We then decompose the uncertainty into that associated with future climate change and that associated with forest resiliency, finding that it is important to reduce the uncertainty in both of these if we are to better determine the Amazon's outcome.


Asunto(s)
Cambio Climático , Modelos Biológicos , Bosque Lluvioso , Incertidumbre , Fotosíntesis , Probabilidad , Estaciones del Año
8.
Nat Commun ; 7: 13667, 2016 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-27922014

RESUMEN

For adaptation and mitigation planning, stakeholders need reliable information about regional precipitation changes under different emissions scenarios and for different time periods. A significant amount of current planning effort assumes that each K of global warming produces roughly the same regional climate change. Here using 25 climate models, we compare precipitation responses with three 2 K intervals of global ensemble mean warming: a fast and a slower route to a first 2 K above pre-industrial levels, and the end-of-century difference between high-emission and mitigation scenarios. We show that, although the two routes to a first 2 K give very similar precipitation changes, a second 2 K produces quite a different response. In particular, the balance of physical mechanisms responsible for climate model uncertainty is different for a first and a second 2 K of warming. The results are consistent with a significant influence from nonlinear physical mechanisms, but aerosol and land-use effects may be important regionally.

9.
Science ; 347(6225): 952, 2015 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-25722400
10.
Philos Trans R Soc Lond B Biol Sci ; 363(1498): 1857-64, 2008 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-18267905

RESUMEN

Simulations with the Hadley Centre general circulation model (HadCM3), including carbon cycle model and forced by a 'business-as-usual' emissions scenario, predict a rapid loss of Amazonian rainforest from the middle of this century onwards. The robustness of this projection to both uncertainty in physical climate drivers and the formulation of the land surface scheme is investigated. We analyse how the modelled vegetation cover in Amazonia responds to (i) uncertainty in the parameters specified in the atmosphere component of HadCM3 and their associated influence on predicted surface climate. We then enhance the land surface description and (ii) implement a multilayer canopy light interception model and compare with the simple 'big-leaf' approach used in the original simulations. Finally, (iii) we investigate the effect of changing the method of simulating vegetation dynamics from an area-based model (TRIFFID) to a more complex size- and age-structured approximation of an individual-based model (ecosystem demography). We find that the loss of Amazonian rainforest is robust across the climate uncertainty explored by perturbed physics simulations covering a wide range of global climate sensitivity. The introduction of the refined light interception model leads to an increase in simulated gross plant carbon uptake for the present day, but, with altered respiration, the net effect is a decrease in net primary productivity. However, this does not significantly affect the carbon loss from vegetation and soil as a consequence of future simulated depletion in soil moisture; the Amazon forest is still lost. The introduction of the more sophisticated dynamic vegetation model reduces but does not halt the rate of forest dieback. The potential for human-induced climate change to trigger the loss of Amazon rainforest appears robust within the context of the uncertainties explored in this paper. Some further uncertainties should be explored, particularly with respect to the representation of rooting depth.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Árboles , Incertidumbre , Predicción , Efecto Invernadero , Luz , Modelos Biológicos , Árboles/fisiología
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