Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay

<p>Abstract</p> <p>Background</p> <p>Nonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed.</p> <p>Results</p> <p>To resolve this issue we examined the properties of putative nonsense-mediated decay targets in humans and mice. We started with a well-annotated set of protein coding genes and found that 2 to 4% of genes are probably subject to nonsense-mediated decay, and that the premature termination codon reflects neither rare mutations nor sequencing artefacts. Several lines of evidence suggested that the noisy splicing model has considerable relevance: 1) exons that are uniquely found in nonsense-mediated decay transcripts (nonsense-mediated decay-specific exons) tend to be newly created; 2) have low-inclusion level; 3) tend not to be a multiple of three long; 4) belong to genes with multiple splice isoforms more often than expected; and 5) these genes are not obviously enriched for any functional class nor conserved as nonsense-mediated decay candidates in other species. However, nonsense-mediated decay-specific exons for which distant orthologous exons can be found tend to have been under purifying selection, consistent with the regulation model.</p> <p>Conclusion</p> <p>We conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.</p

Evidence for common short natural trans sense-antisense pairing between transcripts from protein coding genes

A computational prediction of human coding RNA trans short sense-antisense pairs suggests that mRNA regulation by other coding transcripts might be a common occurrence

Cefquinome Controlled Size Submicron Particles Precipitation by SEDS Process Using Annular Gap Nozzle

An annular gap nozzle was applied in solution enhanced dispersion by supercritical fluids (SEDS) process to prepare cefquinome controlled size submicron particles so as to enhance their efficacy. Analysis results of orthogonal experiments indicated that the concentration of solution was the primary factor to affect particle sizes in SEDS process, and feeding speed of solution, precipitation pressure, and precipitation temperature ranked second to fourth. Meanwhile, the optimal operating conditions were that solution concentration was 100 mg/mL, feeding speed was 9 mL/min, precipitation pressure was 10 MPa, and precipitation temperature was 316 K. The confirmatory experiment showed that D50 of processed cefquinome particles in optimal operating conditions was 0.73 μm. Moreover, univariate effect analysis showed that the cefquinome particle size increased with the increase of concentration of the solution or precipitation pressure but decreased with the increase of solution feeding speed. When precipitation temperature increased, the cefquinome particle size showed highest point. Moreover, characterization of processed cefquinome particles was analyzed by SEM, FT-IR, and XRD. Analysis results indicated that the surface appearance of processed cefquinome particles was flakes. The chemical structure of processed cefquinome particles was not changed, and the crystallinity of processed cefquinome particles was a little lower than that of raw cefquinome particles

Preparation of Cefquinome Nanoparticles by Using the Supercritical Antisolvent Process

The supercritical antisolvent process was used successfully to prepare nanoparticles of cefquinome. These particles were observed by scanning electron microscope (SEM) and their average diameter was measured by laser particle size analyzer. In the experiments, dimethyl sulfoxide (DMSO) was selected as solvent to dissolve cefquinome sulfate. It was confirmed by orthogonal experiments that the concentration of solution was the primary factor in this process followed by feeding speed of solution, precipitation pressure, and precipitation temperature. Moreover, the optimal conditions of preparing nanoparticles of cefquinome by supercritical antisolvent process were that solution concentration was 100 mg/mL, solution flow speed was 1.5 mL/min, operating pressure was 13 Mpa, and operating temperature was 33°C. Confirmatory experiment was conducted under this condition. It was found that the appearance of particles was flakes and the average diameter of particles was 0.71 microns. Finally, influence law of individual factor on particle size was investigated by univariate analysis

Alternative Promoters Influence Alternative Splicing at the Genomic Level

Background: More and more experiments have shown that transcription and mRNA processing are not two independent events but are tightly coupled to each other. Both promoter and transcription rate were found to influence alternative splicing. More than half of human genes have alternative promoters, but it is still not clear why there are so many alternative promoters and what their biological roles are. Methodology/Principal Findings: In this study, we explored whether there is a functional correlation between alternative promoters and alternative splicing by a genome-wide analysis of human and mouse genes. We constructed a large data set of genes with alternative promoter and alternative splicing annotations. By analyzing these genes, we showed that genes with alternative promoters tended to demonstrate alternative splicing compare to genes with single promoter, and, genes with more alternative promoters tend to have more alternative splicing variants. Furthermore, transcripts from different alternative promoters tended to splice differently. Conclusions/Significance: Thus at the genomic level, alternative promoters are positively correlated with alternativ

Establishment of the Predicting Models of the Dyeing Effect in Supercritical Carbon Dioxide Based on the Generalized Regression Neural Network and Back Propagation Neural Network

With the growing demand of supercritical carbon dioxide (SC-CO2) dyeing, it is important to precisely predict the dyeing effect of supercritical carbon dioxide. In this work, Generalized Regression Neural Network (GRNN) and Back Propagation Neural Network (BPNN) models have been employed to predict the dyeing effect of SC-CO2. These two models have been constructed based on published experimental data and calculated values. A total of 386 experimental data sets were used in the present work. In GRNN and BPNN models, two input parameters, such as temperature, pressure, dye stuff types, carrier types and dyeing time, were selected for the input layer and one variable, K/S value or dye-uptake, was used in the output layer. It was found that the values of mean-relative-error (MRE) for BPNN model and for GRNN model are 3.27&ndash;6.54% and 1.68&ndash;3.32%, respectively. The results demonstrate that both BPNN and GPNN models can accurately predict the effect of supercritical dyeing but the former is better than the latter

Bacterial and diazotrophic diversities of endophytes in Dendrobium catenatum determined through barcoded pyrosequencing.

As an epiphyte orchid, Dendrobium catenatum relies on microorganisms for requisite nutrients. Metagenome pyrosequencing based on 16S rRNA and nifH genes was used to characterize the bacterial and diazotrophic communities associated with D. catenatum collected from 5 districts in China. Based on Meta-16S rRNA sequencing, 22 bacterial phyla and 699 genera were identified, distributed as 125 genera from 8 phyla and 319 genera from 10 phyla shared by all the planting bases and all the tissues, respectively. The predominant Proteobacteria varied from 71.81% (GZ) to 96.08% (YN), and Delftia (10.39-38.42%), Burkholderia (2.71-15.98%), Escherichia/Shigella (4.90-25.12%), Pseudomonas (2.68-30.72%) and Sphingomonas (1.83-2.05%) dominated in four planting bases. Pseudomonas (17.94-22.06%), Escherichia/Shigella (6.59-11.59%), Delftia (9.65-22.14%) and Burkholderia (3.12-11.05%) dominated in all the tissues. According to Meta-nifH sequencing, 4 phyla and 45 genera were identified, while 17 genera and 24 genera from 4 phyla were shared by all the planting bases and all the tissues, respectively. Burkholderia and Bradyrhizobium were the most popular in the planting bases, followed by Methylovirgula and Mesorhizobium. Mesorhizobium was the most popular in different tissues, followed by Beijerinckia, Xanthobacter, and Burkholderia. Among the genera, 39 were completely overlapped with the results based on the 16S rRNA gene. In conclusion, abundant bacteria and diazotrophs were identified in common in different tissues of D. catenatum from five planting bases, which might play a great role in the supply of nutrients such as nitrogen. The exact abundance of phylum and genus on the different tissues from different planting bases need deeper sequencing with more samples

An Intelligent Multi-Sensor Variable Spray System with Chaotic Optimization and Adaptive Fuzzy Control

During the variable spray process, the micro-flow control is often held back by such problems as low initial sensitivity, large inertia, large hysteresis, nonlinearity as well as the inevitable difficulties in controlling the size of the variable spray droplets. In this paper, a novel intelligent double closed-loop control with chaotic optimization and adaptive fuzzy logic is developed for a multi-sensor based variable spray system, where a Bang-Bang relay controller is used to speed up the system operation, and adaptive fuzzy nonlinear PID is employed to improve the accuracy and stability of the system. With the chaotic optimization of controller parameters, the system is globally optimized in the whole solution space. By applying the proposed double closed-loop control, the variable pressure control system includes the pressure system as the inner closed-loop and the spray volume system as the outer closed-loop. Thus, the maximum amount of spray droplets deposited on the plant surface may be achieved with the minimum medicine usage for plants. Multiple sensors (for example: three pressure sensors and two flow rate sensors) are employed to measure the system states. Simulation results show that the chaotic optimized controller has a rise time of 0.9 s, along with an adjustment time of 1.5 s and a maximum overshoot of 2.67% (in comparison using PID, the rise time is 2.2 s, the adjustment time is 5 s, and the maximum overshoot is 6.0%). The optimized controller parameters are programmed into the hardware to control the established variable spray system. The experimental results show that the optimal spray pressure of the spray system is approximately 0.3 MPa, and the flow rate is approximately 0.08 m3/h. The effective droplet rate is 89.4%, in comparison to 81.3% using the conventional PID control. The proposed chaotically optimized composite controller significantly improved the dynamic performance of the control system, and satisfactory control results are achieved

Molecular-level investigation of plasticization of polyethylene terephthalate (PET) in supercritical carbon dioxide via molecular dynamics simulation

The current study aims to use the molecular dynamics (MD) simulation method to discuss the glass transition behaviour and fractional free volume (FFV) of the pure polyethylene terephthalate (PET) and the plasticized PET induced by supercritical carbon dioxide (SC-CO2) sorption. The adsorption concentration reproduced through sorption relaxation cycles (SRC) was firstly estimated and in an order of magnitude with the known experimental results available in the reported literature. The FFV induced by SC-CO2 in PET polymer changes regularly, which is proportional to the capacity of SC-CO2 adsorption with the changes in temperature and pressure. The glass transition temperature (Tg) was further estimated to be almost identical to the known experimental values and shows a gradually decreasing tendency with the increase of pressure. Meanwhile, the plasticization of PET polymer studied by radial distribution functions showed that CO2 molecules occupying the sorption sites on the PET backbone promoted plasticization by increasing the fluidity of the PET backbone chain