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

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

Hierarchical porous carbon with ordered straight micro-channels templated by continuous filament glass fiber arrays for high performance supercapacitors

Hierarchical porous carbon with highly ordered straight micro-channels was prepared though a facile melt vacuum infiltration method using continuous filament glass fiber arrays as the template and glucose as the precursor. The as-prepared carbon material shows high specific surface areas up to 1880 m2 g�1 profited from the unique structure of straight micro-channels. A fine pore structure is formed in the channel wall through KOH activation after the removal of the glass fiber array. electrochemical evaluation of the carbon material indicates that the hierarchical porous carbon exhibits a high specific capacitance of 283 F g�1 at a current density of 0.25 A g�1 with an alkaline electrolyte (6 M KOH) in a threeelectrode system. It also demonstrates excellent cycling stability with a capacity retention of 88.5% over 10 000 cycles at a high current density of 6 A g�1. These exciting results demonstrate a very simple and low-cost method for large-scale preparation of electrode materials for supercapacitors

Research Progress on Pole-Climbing Robots: A Review

Background: Pole-climbing robots are a type of application robot commonly used for quality inspection, cleaning, and maintenance of utility poles, high voltage lines, bridge cables, transmission pipelines, and other important facilities with a certain height. The working conditions are often harsh and dangerous, making manual participation unsafe. The pole-climbing robot can provide a platform for maintenance and cleaning work. Remote control operation of the pole-climbing robot is achieved through communication and control technology. It has been created to improve efficiency and reduce personnel accidents greatly. At the same time, the continuous development of science and technology has led to the expansion of robot design concepts. It has also brought about great changes and growth in the development of pole-climbing robots. Objective: The purpose of this paper is to report the latest progress in the research of pole-climbing robots from bionic and non-bionic perspectives and to provide a research reference for researchers in this field. Method: By analyzing academic theses and published patents, this paper presents a new classification of pole-climbing robots from the perspective of bionic and non-bionic. By summarizing the literature, the structural characteristics of various pole-climbing robots and their differences and applications are summarized. Results: The performance of the pole-climbing robots is analyzed from the viewpoint of structural characteristics and action execution methods. In turn, the characteristics of various types of pole-climbing robots are summarized. Finally, based on the above discussion, the future problems and development directions of pole-climbing robots are predicted. Conclusion: The pole-climbing robots can be divided into two categories, bionic and non-bionic, based on the analysis of design features. Both bionic and non-bionic pole-climbing robots have good development and applications in their respective directions. Also, bionic and non-bionic pole-climbing robots have different detailed classifications based on material, structure, and other perspectives. They have different advantages and disadvantages in terms of the performance of pole-climbing action execution. It provides a research reference for future researchers in this field

Insulin promotes progression of colon cancer by upregulation of ACAT1

Abstract Background Insulin resistant and the progression of cancer is closely related. The aim of this study was to  investigate the effect of insulin on the proliferation and migration of colon cancer cells and its underlying mechanism. Methods Colon carcinoma tissues from the 80 cases of colon cancer patients were collected. Immunohistochemistry was used to detect the expression of acyl coenzyme A: cholesterol acyltransferase1 (ACAT1), and we analyzed the correlation between hyperglycemia and ACAT1, hyperglycemia and metastasis. CCK8 assay and transwell assay were used to investigate the effect of different concentrations of insulin and ACAT1siRNA on human colon cancer cell line HT-29. ACAT1 mRNA expression and protein level in HT-29 cells were determined by real-time quantitative PCR and western blotting, respectively. Results Biopsies from patients with colon carcinoma showed hyperglycemia links ACAT1, lymph nodes metastasis and distant metastasis. Insulin markedly promoted cell proliferation and migration in human colon cancer HT-29 cells. Moreover, ACAT1mRNA expression and protein level were increased by insulin. ACAT1siRNA resulted in a complete inhibition of the ACAT1 mRNA expression. Consequently insulin-triggered cell proliferation and migration on colon cancer cells were inhibited. Conclusion The progression of colon cancer has a positive correlation with hyperinsulinemia. Insulin-triggered cell proliferation and metastatic effects on colorectal cancer cells are mediated by ACAT1. Therefore, insulin could promote colon cancer progression by upregulation of ACAT1, which maybe is a potential therapeutic target for colon cancer

Autophagy Is Indispensable for the Self-Renewal and Quiescence of Ovarian Cancer Spheroid Cells with Stem Cell-Like Properties

Epithelial ovarian cancer has the highest mortality rate of all gynecologic cancers. Cancer stem cells are considered to be the initiating cells of tumors. It is known that spheroid culture promotes ovarian cancer cells to acquire stem cell characteristics and to become stem cell-like. But the mechanisms remain largely unclear. Our data show that autophagy is sustainably activated in ovarian cancer spheroid cells. Inhibition of autophagy by knockdown of ATG5 abolishes the self-renewal ability of ovarian cancer spheroid cells. Knockdown of ATG5 prevents ovarian cancer spheroid cells to enter quiescent state. Autophagy is critical for quiescent ovarian cancer spheroid cells to reenter the cell cycle because rapamycin can promote quiescent ovarian cancer spheroid cells to form colonies on soft agar and knockdown of ATG5 can arrest ovarian cancer cells in G0/G1. Autophagy and NRF2 form a positive feedback regulation loop to regulate reactive oxygen species (ROS) levels in ovarian cancer spheroid cells. The optimal ROS level, neither too high nor too low, facilitates the self-renewal marker, NOTCH1, to reach to the highest level. Bafilomycin A1 can impair the self-renewal of ovarian cancer spheroid cells by disturbing ROS levels

A Depth-Based Weighted Point Cloud Registration for Indoor Scene

Point cloud registration plays a key role in three-dimensional scene reconstruction, and determines the effect of reconstruction. The iterative closest point algorithm is widely used for point cloud registration. To improve the accuracy of point cloud registration and the convergence speed of registration error, point pairs with smaller Euclidean distances are used as the points to be registered, and the depth measurement error model and weight function are analyzed. The measurement error is taken into account in the registration process. The experimental results of different indoor scenes demonstrate that the proposed method effectively improves the registration accuracy and the convergence speed of registration error

Transcriptome analysis of Xanthomonas oryzae pv. oryzicola exposed to H2O2 reveals horizontal gene transfer contributes to its oxidative stress response.

Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of bacterial leaf streak, is one of the most severe seed-borne bacterial diseases of rice. However, the molecular mechanisms underlying Xoc in response to oxidative stress are still unknown. In this study, we performed a time-course RNA-seq analysis on the Xoc in response to H2O2, aiming to reveal its oxidative response network. Overall, our RNA sequence analysis of Xoc revealed a significant global gene expression profile when it was exposed to H2O2. There were 7, 177, and 246 genes that were differentially regulated at the early, middle, and late stages after exposure, respectively. Three genes (xoc_1643, xoc_1946, xoc_3249) showing significantly different expression levels had proven relationships with oxidative stress response and pathogenesis. Moreover, a hypothetical protein (XOC_2868) showed significantly differential expression, and the xoc_2868 mutants clearly displayed a greater H2O2 sensitivity and decreased pathogenicity than those of the wild-type. Gene localization and phylogeny analysis strongly suggests that this gene may have been horizontally transferred from a Burkholderiaceae ancestor. Our study not only provides a first glance of Xoc's global response against oxidative stress, but also reveals the impact of horizontal gene transfer in the evolutionary history of Xoc