Transcriptional elongation defects enhance upstream poly (A) site utilization and SPT5 affects mRNA degradation through its physical and functional interaction with CCR4 -NOT complex

While a number of proteins are involved in elongational processes, the mechanism of action of most of these factors remains unclear primarily because of the lack of suitable in vivo model systems. We have identified in yeast several genes, each of which contain internal poly (A) sites, whose full-length mRNA formation is reduced by mutations in RNA polymerase II subunit RPB2, elongation factor SPT5, or TFIIS. RPB2 and SPT5 defects also promoted the utilization of upstream poly (A) sites for genes that contain multiple 3 \u27 poly (A) signaling sequences, supporting a role for elongation in differential poly (A) site choice. Our data suggest that elongation defects cause increased transcriptional pausing or arrest that results in increased utilization of internal or upstream poly (A) sites. Transcriptional pausing/arrest can, therefore, be visualized in vivo if a gene contains internal poly (A) sites, allowing biochemical and genetic study of the elongation process. The CCR4-NOT complex has been shown to have role in transcriptional initiation, elongation, and mRNA degradation with the primary role of CCR4 and CAF1 in the deadenylation and degradation of mRNA. Previous work in our lab has identified a physical connection between the CCR4-NOT complex and SPT5. The role of SPT5 in mRNA degradation was examined. Mutation in SPT5 or an spt4 deletion slowed the rate of mRNA degradation, a phenotype associated with defects in the CCR4 and CAF1 mRNA deadenylase complex. Moreover, like ccr4 and caf1 deletion, spt5 and spt4 defects affected the rate of deadenylation, but not that of decapping or 5\u27-3\u27 degradation of mRNA. Re-examination of SPT5 location in the yeast cell confirmed that SPT5 is primarily nuclear but some SPT5 was also found to locate to the cytoplasm. These results support a role for SPT5/SPT4 in mRNA degradation through inhibition of CCR4 deadenylase activity

SPT5 affects the rate of mRNA degradation and physically interacts with CCR4 but does not control mRNA deadenylation

The CCR4-NOT complex has been shown to have multiple roles in mRNA metabolism, including that of transcriptional elongation, mRNA transport, and nuclear exosome function, but the primary function of CCR4 and CAF1 is in the deadenylation and degradation of cytoplasmic mRNA. As previous genetic analysis supported an interaction between SPT5, known to be involved in transcriptional elongation, and that of CCR4, the physical association of SPT5 with CCR4 was examined. A two-hybrid screen utilizing the deadenylase domain of CCR4 as a bait identified SPT5 as a potential interacting protein. SPT5 at its physiological concentration was shown to immunoprecipitate CCR4 and CAF1, and in vitro purified SPT5 specifically could bind to CAF1 and the deadenylase domain of CCR4. We additionally demonstrated that mutations in SPT5 or an spt4 deletion slowed the rate of mRNA degradation, a phenotype associated with defects in the CCR4 mRNA deadenylase complex. Yet, unlike ccr4 and caf1 deletions, spt5 and spt4 defects displayed little effect on the rate of deadenylation. They also did not affect decapping or 5\u27 - 3\u27 degradation of mRNA. These results suggest that the interactions between SPT5/SPT4 and the CCR4-NOT complex are probably the consequences of effects involving nuclear events and do not involve the primary role of CCR4 in mRNA deadenylation and turnover

Langerhans cell histiocytosis in the jugular foramen

Langerhans cell histiocytosis (LCH) is a rare disease of neoplastic proliferation of monocyte–macrophage system. Although LCH can affect almost any organ, solitary involvement of jugular foramen is extremely rare and can present a diagnostic dilemma because of its rarity at this location. Here, we present the case of an adult patient with LCH affecting the jugular foramen, and review the relevant literature

Seasonal fluxes and sources apportionment of dissolved inorganic nitrogen wet deposition at different land-use sites in the Three Gorges reservoir area.

To identify seasonal fluxes and sources of dissolved inorganic nitrogen (DIN) wet deposition, concentrations and δ15N signatures of nitrate (NO3−) and ammonium (NH4+) in wet precipitation were measured at four typical land-use types in the Three Gorges reservoir (TGR) area of southwest China for a one-year period. Higher DIN fluxes were recorded in spring and summer and their total fluxes (averaged 7.58 kg N ha−1) were similar to the critical loads in aquatic ecosystems. Significant differences of precipitation δ15N were observed for NH4+-N between town and wetland sites in spring and between urban and rural sites in summer. For NO3−-N, significant differences of precipitation δ15N were observed between town and rural sites in spring and between urban and town sites in autumn, respectively. Quantitative results of NO3−-N sources showed that both biomass burning and coal combustion had higher fluxes at the urban site especially in winter (0.18 ± 0.09 and 0.19 ± 0.08 kg N ha−1), which were about three times higher than those at the town site. A similar finding was observed for soil emission and vehicle exhausts in winter. On the whole, DIN wet deposition averaged at 12.13 kg N ha−1 yr−1 with the urban site as the hotspot (17.50 kg N ha−1 yr−1) and regional NO3−-N fluxes had a seasonal pattern with minimum values in winter. The contribution to NO3−-N wet deposition from biomass burning was 26.1 ± 14.1%, which is the second dominant factor lower than coal combustion (26.5 ± 12.6%) in the TGR area during spring and summer. Hence N emission reduction from biomass burning, coal combustion and vehicle exhausts should be strengthened especially in spring and summer to effectively manage DIN pollution for the sustainable development in TGR area

Heterogeneous characters modeling of instant message services users’ online behavior

Research on temporal characteristics of human dynamics has attracted much attentions for its contribution to various areas such as communication, medical treatment, finance, etc. Existing studies show that the time intervals between two consecutive events present different non-Poisson characteristics, such as power-law, Pareto, bimodal distribution of power-law, exponential distribution, piecewise power-law, et al. With the occurrences of new services, new types of distributions may arise. In this paper, we study the distributions of the time intervals between two consecutive visits to QQ and WeChat service, the top two popular instant messaging services in China, and present a new finding that when the value of statistical unit T is set to 0.001s, the inter-event time distribution follows a piecewise distribution of exponential and power-law, indicating the heterogeneous character of IM services users’ online behavior in different time scales. We infer that the heterogeneous character is related to the communication mechanism of IM and the habits of users. Then we develop a combination model of exponential model and interest model to characterize the heterogeneity. Furthermore, we find that the exponent of the inter-event time distribution of the same service is different in two cities, which is correlated with the popularity of the services. Our research is useful for the application of information diffusion, prediction of economic development of cities, and so on.National Natural Science Foundation (China) (61201153)National Basic Research Program of China (973 Program) (Grant 2012CB315805)CCF Venus Research Project (CCF-VenustechRP2016004)Jiangsu Industrial Technology Research Institute. Institute of Future Networks Technology (BY2013095-2-16

Mechanism and Role of Tumor Microenvironment in the Initiation and Progression of Bladder Cancer

Tumor microenvironment (TME) is a huge network, composed by tumor cells, tumor associated stromal cells, immune cells, cytokines and chemokines secreted by these cells, in which various cells communicate with each other. Bladder cancer is characterized of tendency of relapse, progression, metastasis because of the role of TME. With the application and development of new technologies recently, such as tumor bulk RNA-sequencing and singlecell transcriptome sequencing, the composition of TME for bladder cancer is increasingly clear and the complex cell-to-cell communication network is fully duged, which provides a new vision for the therapy of bladder cancer. This paper reviewed and further analysed the research hotspots of cellular components and extracellular matrix components of bladder cancer on the basis of the latest research progress

A Review on Kentucky Bluegrass Responses and Tolerance to Drought Stress

Kentucky bluegrass (Poa pratensis L.) is an excellent cool-season turfgrass and is extensively used in urban green space, parks and sports fields worldwide, but it is sensitive to drought stress. Drought reduces turf quality of Kentucky bluegrass by influences on the shoot density, texture, uniformity, color, growth habit and recuperative capacity. It has been a challenge for breeding water saving cultivars and enhances water use efficiency in Kentucky bluegrass. Many studies have revealed the mechanisms of drought stress tolerance in Kentucky bluegrass via multiple approaches. The morphological and physiological attributes as well as molecular information were discovered for better understanding and improving its drought tolerance. In this chapter, we will draw a systematic literature review about Kentucky bluegrass in response to drought stress and provide future perspectives of Kentucky bluegrass drought resistance research

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism