Decay Dynamics of Tumors.
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ABSTRACT:
SUBMITTER: Lopez AG
PROVIDER: S-EPMC4910984 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:It is generally assumed that mRNAs undergoing translation are protected from decay. Here, we show that mRNAs are, in fact, co-translationally degraded. This is a widespread and conserved process affecting most genes, where 5'-3' transcript degradation follows the last translating ribosome, producing an in vivo ribosomal footprint. By sequencing the ends of 5' phosphorylated mRNA degradation intermediates, we obtain a genome-wide drug-free measurement of ribosome dynamics. We identify general translation termination pauses in both normal and stress conditions. In addition, we describe novel codon-specific ribosomal pausing sites in response to oxidative stress that are dependent on the RNase Rny1. Our approach is simple and straightforward and does not require the use of translational inhibitors or in vitro RNA footprinting that can alter ribosome protection patterns.
| S-EPMC4461875 | biostudies-literature
Project description:It is generally assumed that mRNAs undergoing translation are protected from decay. Here, we show that mRNAs are, in fact, co-translationally degraded. This is a widespread and conserved process affecting most genes, where 5′–3′ transcript degradation follows the last translating ribosome, producing an in vivo ribosomal footprint. By sequencing the ends of 5′ phosphorylated mRNA degradation intermediates, we obtain a genome-wide drug-free measurement of ribosome dynamics. We identify general translation termination pauses in both normal and stress conditions. In addition, we describe novel codon-specific ribosomal pausing sites in response to oxidative stress that are dependent on the RNase Rny1. Our approach is simple and straightforward and does not require the use of translational inhibitors or in vitro RNA footprinting that can alter ribosome protection patterns. RNA samples were quantified according to their 5’modification. Samples were quantified using 2 alternative methods. 5PSeq (measures 5’P RNAs) and 5PSeq-fragmented (measures the sequencing bias present in any sample by randomly fragmenting RNA, re-phosphorilating the 5’ends and subjecting the sample to 5PSeq; it is used as a negative control). Different strains of S. cerevisiae and S. pombe samples were analyzed. Cells were grown both in rich media (YPD or YES) and synthetic defined media (SD). Cells were subjected to different treatments such as inhibition of translation elongation with cyclohexamide (CHX), oxidative stress (0.2 mM H2O2) or inhibition of histidine biosyntesys (3-AT; 100mM 3-amino-1,2,4-triazole). S. cerevisiae samples grown in rich media were also analyzed after CHX treatment and sucrose fractionation into monosome and polyribosome fractionation. All samples were analyzed in biological duplicates.
2015-06-04 | E-GEOD-63120 | biostudies-arrayexpress
Project description:Under the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual-based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community-driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions.
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Project description:BackgroundThe majority of wood decomposing fungi are mushroom-forming Agaricomycetes, which exhibit two main modes of plant cell wall decomposition: white rot, in which all plant cell wall components are degraded, including lignin, and brown rot, in which lignin is modified but not appreciably removed. Previous studies suggested that brown rot fungi tend to be specialists of gymnosperm hosts and that brown rot promotes gymnosperm specialization. However, these hypotheses were based on analyses of limited datasets of Agaricomycetes. Overcoming this limitation, we used a phylogeny with 1157 species integrating available sequences, assembled decay mode characters from the literature, and coded host specialization using the newly developed R package, rusda.ResultsWe found that most brown rot fungi are generalists or gymnosperm specialists, whereas most white rot fungi are angiosperm specialists. A six-state model of the evolution of host specialization revealed high transition rates between generalism and specialization in both decay modes. However, while white rot lineages switched most frequently to angiosperm specialists, brown rot lineages switched most frequently to generalism. A time-calibrated phylogeny revealed that Agaricomycetes is older than the flowering plants but many of the large clades originated after the diversification of the angiosperms in the Cretaceous.ConclusionsOur results challenge the current view that brown rot fungi are primarily gymnosperm specialists and reveal intensive white rot specialization to angiosperm hosts. We thus suggest that brown rot associated convergent loss of lignocellulose degrading enzymes was correlated with host generalism, rather than gymnosperm specialism. A likelihood model of host specialization evolution together with a time-calibrated phylogeny further suggests that the rise of the angiosperms opened a new mega-niche for wood-decay fungi, which was exploited particularly well by white rot lineages.
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Project description:Inflammatory myofibroblastic tumors (IMTs) are characterized by myofibroblast proliferation and an inflammatory cell infiltrate. Little is known about the molecular pathways that precipitate IMT formation. Here, we report the identification of somatic mutations in UPF1, a gene that encodes an essential component of the nonsense-mediated RNA decay (NMD) pathway, in 13 of 15 pulmonary IMT samples. The majority of mutations occurred in a specific region of UPF1 and triggered UPF1 alternative splicing. Several mRNA targets of the NMD pathway were upregulated in IMT samples, indicating that the UPF1 mutations led to reduced NMD magnitude. These upregulated NMD targets included NIK mRNA, which encodes a potent activator of NF-?B. In human lung cells, UPF1 depletion increased expression of chemokine-encoding genes in a NIK-dependent manner. Elevated chemokines and IgE class switching events were observed in IMT samples, consistent with NIK upregulation in these tumors. Together, these results support a model in which UPF1 mutations downregulate NMD, leading to NIK-dependent NF-?B induction, which contributes to the immune infiltration that is characteristic of IMTs. The molecular link between the NMD pathway and IMTs has implications for the diagnosis and treatment of these tumors.
| S-EPMC4966300 | biostudies-literature
Project description:It is generally assumed that mRNAs undergoing translation are protected from decay. Here, we show that mRNAs are, in fact, co-translationally degraded. This is a widespread and conserved process affecting most genes, where 5′–3′ transcript degradation follows the last translating ribosome, producing an in vivo ribosomal footprint. By sequencing the ends of 5′ phosphorylated mRNA degradation intermediates, we obtain a genome-wide drug-free measurement of ribosome dynamics. We identify general translation termination pauses in both normal and stress conditions. In addition, we describe novel codon-specific ribosomal pausing sites in response to oxidative stress that are dependent on the RNase Rny1. Our approach is simple and straightforward and does not require the use of translational inhibitors or in vitro RNA footprinting that can alter ribosome protection patterns.
2015-06-04 | GSE63120 | GEO
Project description:Proper transcriptome reprogramming is critical for hosts to launch an effective defense response upon pathogen attack. How immune-related genes are regulated at the posttranscriptional level remains elusive. We demonstrate here that P-bodies, the non-membranous cytoplasmic ribonucleoprotein foci related to 5'-to-3' mRNA decay, are dynamically modulated in plant immunity triggered by microbe-associated molecular patterns (MAMPs). The DCP1-DCP2 mRNA decapping complex, a hallmark of P-bodies, positively regulates plant MAMP-triggered responses and immunity against pathogenic bacteria. MAMP-activated MAP kinases directly phosphorylate DCP1 at the serine237 residue, which further stimulates its interaction with XRN4, an exonuclease executing 5'-to-3' degradation of decapped mRNA. Consequently, MAMP treatment potentiates DCP1-dependent mRNA decay on a specific group of MAMP-downregulated genes. Thus, the conserved 5'-to-3' mRNA decay elicited by the MAMP-activated MAP kinase cascade is an integral part of plant immunity. This mechanism ensures a rapid posttranscriptional downregulation of certain immune-related genes that may otherwise negatively impact immunity.
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Project description:One aspect of earthquake physics not adequately addressed is why some earthquakes generate thousands of aftershocks while other earthquakes generate few, if any, aftershocks. It also remains unknown why aftershock rates decay as ~1/time. Here, I show that these two are linked, with a dearth of aftershocks reflecting the absence of high-pressure fluid sources at depth, while rich and long-lasting aftershock sequences reflect tapping high-pressure fluid reservoirs that drive aftershock sequences. Using a physical model that captures the dominant aspects of permeability dynamics in the crust, I show that the model generates superior fits to observations than widely used empirical fits such as the Omori-Utsu Law, and find a functional relationship between aftershock decay rates and the tectonic ability to heal the co- and post-seismically generated fracture networks. These results have far-reaching implications, and can help interpret other observations such as seismic velocity recovery, attenuation, and migration.
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