mRNA Surveillance Pathway Research Articles

Chronic Hypobaric Hypoxia Stimulates Differential Expression of Cognitive Proteins in Hippocampal Tissue.

Objective: We aimed to determine changes in cognitive function resulting from chronic hypobaric hypoxia through proteomic analysis of hippocampal tissue. We screened cognition-related proteins to provide ideas and directions that could help prevent and treat hypoxia-associated cognitive impairment. Methods: We analyzed hippocampal tissues from mice exposed to high altitudes and control mice using 4 D label-free quantitative proteomics. The data were analyzed by protein quantitative analysis, functional annotation, differential protein screening, clustering analyses, and functional classification and enrichment. Differential protein expression was investigated using targeted quantitative omics based on parallel response monitoring. Results: We identified and quantified 20 target proteins in 12 samples, of which 18 were significant validated proteins that were or might be related to cognitive functions. Signaling pathways that were significantly enriched in differentially expressed proteins were pyrimidine metabolism, 5'-Adenosine Triphosphate-activated protein kinase signaling, phospholipase D signaling, purine metabolism, inflammatory mediator regulation of transient receptor potential channels, hedgehog signaling pathways, dilated cardiomyopathy, platelet activation, insulin resistance, mRNA surveillance pathways, drug metabolism-other enzymes, and drug metabolism-cytochrome P450. Conclusion: Chronic hypoxia alters protein expression in murine hippocampal tissues. Eighteen differentially expressed cognition-related proteins might be related to cognitive impairment in mice exposed to chronic high-altitude hypoxia.

Prognostic Relevance of Copy Number Losses in Ovarian Cancer.

Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients' prognosis. Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients' prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers.

Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy.

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5' splice sites. Disruptive cryptic variants evaded messenger RNA (mRNA) surveillance pathways and were translated into misfolded proteins, which caused proteotoxic aggregates, endoplasmic reticulum (ER) stress, and, ultimately, cell death. The detrimental consequence of splicing-induced proteotoxicity could be mitigated by up-regulating the ubiquitin-proteasome system and selective autophagy. Our findings provide insight into the molecular pathogenesis of spliceosome-associated diseases.

Maize splicing-mediated mRNA surveillance impeded by sugarcane mosaic virus-coded pathogenic protein NIa-Pro.

The eukaryotic mRNA surveillance pathway, a pivotal guardian of mRNA fidelity, stands at the nexus of diverse biological processes, including antiviral immunity. Despite the recognized function of splicing factors on mRNA fate, the intricate interplay shaping the mRNA surveillance pathway remains elusive. We illustrate that the conserved splicing factor U2 snRNP auxiliary factor large subunit B (U2AF65B) modulates splicing of mRNA surveillance complex, contributing to transcriptomic homeostasis in maize. The functionality of the mRNA surveillance pathway requires ZmU2AF65B-mediated normal splicing of upstream frameshift 3 (ZmUPF3) pre-mRNA, encoding a core factor in this pathway. Intriguingly, sugarcane mosaic virus (SCMV)-coded nuclear inclusion protein a protease (NIa-Pro) hinders the splicing function of ZmU2AF65B. Furthermore, NIa-Pro disrupts ZmU2AF65B binding to ZmUPF3 pre-mRNA, leading to dysregulated splicing of ZmUPF3 transcripts and, consequently, impairing mRNA surveillance, thus facilitating viral infection. Together, this study establishes that splicing governs the mRNA surveillance pathway and identifies a pathogenic protein capable of disrupting this regulation to compromise RNA immunity.

Regulatory microRNAs and phasiRNAs of paclitaxel biosynthesis in Taxus chinensis.

Paclitaxel (trade name Taxol) is a rare diterpenoid with anticancer activity isolated from Taxus. At present, paclitaxel is mainly produced by the semi-synthetic method using extract of Taxus tissues as raw materials. The studies of regulatory mechanisms in paclitaxel biosynthesis would promote the production of paclitaxel through tissue/cell culture approaches. Here, we systematically identified 990 transcription factors (TFs), 460 microRNAs (miRNAs), and 160 phased small interfering RNAs (phasiRNAs) in Taxus chinensis to explore their interactions and potential roles in regulation of paclitaxel synthesis. The expression levels of enzyme genes in cone and root were higher than those in leaf and bark. Nearly all enzyme genes in the paclitaxel synthesis pathway were significantly up-regulated after jasmonate treatment, except for GGPPS and CoA Ligase. The expression level of enzyme genes located in the latter steps of the synthesis pathway was significantly higher in female barks than in male. Regulatory TFs were inferred through co-expression network analysis, resulting in the identification of TFs from diverse families including MYB and AP2. Genes with ADP binding and copper ion binding functions were overrepresented in targets of miRNA genes. The miRNA targets were mainly enriched with genes in plant hormone signal transduction, mRNA surveillance pathway, cell cycle and DNA replication. Genes in oxidoreductase activity, protein-disulfide reductase activity were enriched in targets of phasiRNAs. Regulatory networks were further constructed including components of enzyme genes, TFs, miRNAs, and phasiRNAs. The hierarchical regulation of paclitaxel production by miRNAs and phasiRNAs indicates a robust regulation at post-transcriptional level. Our study on transcriptional and posttranscriptional regulation of paclitaxel synthesis provides clues for enhancing paclitaxel production using synthetic biology technology.

UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.

Nonsense-mediated mRNA decay (NMD) is a conserved co-translational mRNA surveillance and turnover pathway across eukaryotes. NMD has a central role in degrading defective mRNAs and also regulates the stability of a significant portion of the transcriptome. The pathway is organized around UPF1, an RNA helicase that can interact with several NMD-specific factors. In human cells, degradation of the targeted mRNAs begins with a cleavage event that requires the recruitment of the SMG6 endonuclease to UPF1. Previous studies have identified functional links between SMG6 and UPF1, but the underlying molecular mechanisms have remained elusive. Here, we used mass spectrometry, structural biology and biochemical approaches to identify and characterize a conserved short linear motif in SMG6 that interacts with the cysteine/histidine-rich (CH) domain of UPF1. Unexpectedly, we found that the UPF1-SMG6 interaction is precluded when the UPF1 CH domain is engaged with another NMD factor, UPF2. Based on cryo-EM data, we propose that the formation of distinct SMG6-containing and UPF2-containing NMD complexes may be dictated by different conformational states connected to the RNA-binding status of UPF1. Our findings rationalize a key event in metazoan NMD and advance our understanding of mechanisms regulating activity and guiding substrate recognition by the SMG6 endonuclease.

Transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae

Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-rearing industry. Whole-transcriptome analyses have revealed non-coding RNAs and their regulatory networks in N. bombycis infected embryos and larvae. However, transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae remains unclear. Here, we simultaneously compared the transcriptomes of N. bombycis and its host B. mori embryos of 5-day and larvae of 1-, 5- and 10-day during congenital infection. For the transcriptome of N. bombycis, a comparison of parasite expression patterns between congenital-infected embryos and larva showed most genes related to parasite central carbon metabolism were down-regulated in larvae during infection, whereas the majority of genes involved in parasite proliferation and growth were up-regulated. Interestingly, a large number of distinct or shared differentially expressed genes (DEGs) were revealed by the Venn diagram and heat map, many of them were connected to infection related factors such as Ricin B lectin, spore wall protein, polar tube protein, and polysaccharide deacetylase. For the transcriptome of B. mori infected with N. bombycis, beyond numerous DEGs related to DNA replication and repair, mRNA surveillance pathway, RNA transport, protein biosynthesis, and proteolysis, with the progression of infection, a large number of DEGs related to immune and infection pathways, including phagocytosis, apoptosis, TNF, Toll-like receptor, NF-kappa B, Fc epsilon RI, and some diseases, were successively identified. In contrast, most genes associated with the insulin signaling pathway, 2-oxacarboxylic acid metabolism, amino acid biosynthesis, and lipid metabolisms were up-regulated in larvae compared to those in embryos. Furthermore, dozens of distinct and three shared DEGs that were involved in the epigenetic regulations, such as polycomb, histone-lysine-specific demethylases, and histone-lysine-N-methyltransferases, were identified via the Venn diagram and heat maps. Notably, many DEGs of host and parasite associated with lipid-related metabolisms were verified by RT-qPCR. Taken together, simultaneous transcriptomic analyses of both host and parasite genes lead to a better understanding of changes in the microsporidia proliferation and host responses in embryos and larvae in N. bombycis congenital infection.

Abstract 3364: PELO is a synthetic lethal target in chromosome 9p21-deleted or MSI cancers

Abstract Homozygous deletion of chromosomal region 9p21.3 is one of the most frequently observed somatic copy number alterations in cancers, occurring in approximately 15% of all cancers. Many of the 9p21.3-deleted cancers are further characterized by poor clinical outcomes including subsets of glioblastoma, pancreatic, esophageal, and urothelial cancers. Large deletions of chromosomal regions may also provide unique therapeutic opportunities. Specifically, cancer-specific therapeutic opportunities can arise from co-deletions of passenger genes neighboring tumor suppressors. As such, we sought to identify novel therapeutic targets associated with Ch9p21.3 loss in cancers and identified the pelota mRNA surveillance and ribosome rescue factor (PELO) as the top preferential dependency in 9p21.3-deleted cancers. Intriguingly in another analysis, we identified PELO to be amongst the top preferential dependencies in cancers with microsatellite instability (MSI), which accounts for subsets of colorectal, endometrial, gastric, and ovarian cancers. Given the strength of PELO as a candidate synthetic lethal target in two distinct cancer subsets, we performed focused validation with CRISPR interference across multiple cell lines. Knockdown of PELO preferentially impaired the viability of MSI or 9p21-deleted as compared to control (9p21-proficient and microsatellite stable) cells. Further validation with patient-derived organoid and in vivo xenograft models confirmed these findings. We next sought to refine the predictive biomarkers for PELO dependency and identified loss of FOCAD (a 9p21.3 gene and an interactor of the SKI mRNA surveillance pathway) as necessary and sufficient for PELO dependency in the 9p21.3-deleted context. Our findings implicate splicing alterations involving TTC37, a key protein in the SKI mRNA surveillance complex, as the underlying cause of PELO dependency in MSI cancers. Together, we found that loss of large deletions of 9p21.3 and MSI independently impair the SKI complex, uncovering a dependency upon PELO and highlighting a novel functional interaction between PELO and the SKI complex. Furthermore, the strength of this synthetic lethal interaction in a broad range of cancers with poor outcomes underscores the potential of PELO as a promising drug target for patients with 9p21.3-deleted or MSI cancers. Citation Format: Edmond M. Chan, Patricia Borck, Nolan Bick, Kristina Jankovic, Isabella Boyle, Lucy Parker-Burns, Kyla Foster, Anthony Lau, Ashir Borah, Joshua Dempster, Francisca Vazquez. PELO is a synthetic lethal target in chromosome 9p21-deleted or MSI cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3364.

Opportunistic pathogens increased and probiotics or short-chain fatty acid-producing bacteria decreased in the intestinal microbiota of pneumonia inpatients during SARS-CoV-2 Omicron variant epidemic.

The global pandemic of COVID-19 has been over four years, and the role of intestinal microbiota in the occurrence and development of COVID-19 needs to be further clarified. During the outbreak of SARS-CoV-2 Omicron variant in China, we analyzed the intestinal microbiome in fecal samples from inpatients with pneumonia and normal individuals in January 2023. The microbiota composition, alpha diversity, beta diversity, differential microbial community, co-occurrence networks, and functional abundance were analyzed. The results showed significant differences in microbiota composition between the two groups. In pneumonia group, the abundance of Bifidobacterium, Blautia, Clostridium, and Coprococcus decreased, while the abundance of Enterococcus, Lactobacillus, and Megamonas increased. Through LEfSe analysis, 37 marker microbiota were identified in pneumonia group. Co-occurrence network analysis found that Lachnospiraceae was critical for the interaction of intestinal microbiota, and the anti-inflammatory bacteria Blautia was negatively correlated with the pro-inflammatory bacteria Ruminococcus. Functional prediction found the up-regulation of steroid biosynthesis, geraniol degradation, and mRNA surveillance pathway in pneumonia group. In conclusion, opportunistic pathogens increased and probiotics, or short-chain fatty acid-producing bacteria, decreased in the intestinal microbiota of pneumonia inpatients during the Omicron epidemic. Blautia could be used as a probiotic in the treatment of pneumonia patients in the future.

Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications.

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved surveillance mechanism in eukaryotes primarily deployed to ensure RNA quality control by eliminating aberrant transcripts and also involved in modulating the expression of several physiological transcripts. NMD, the mRNA surveillance pathway, is a major form of gene regulation in eukaryotes. NMD serves as one of the most significant quality control mechanisms as it primarily scans the newly synthesized transcripts and differentiates the aberrant and non-aberrant transcripts. The synthesis of truncated proteins is restricted, which would otherwise lead to cellular dysfunctions. The up-frameshift factors (UPFs) play a central role in executing the NMD event, largely by recognizing and recruiting multiple protein factors that result in the decay of non-physiological mRNAs. NMD exhibits astounding variability in its ability across eukaryotes in an array of pathological and physiological contexts. The detailed understanding of NMD and the underlying molecular mechanisms remains blurred. This review outlines our current understanding of NMD, in regulating multifaceted cellular events during development and disease. It also attempts to identify unanswered questions that deserve further investigation.

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.

Timeless is well-known for its key role in replication checkpoints. Recent studies reveal the involvement of Timeless and specificity protein (SP) 1 in human malignancies. However, no evidence proved the interaction between SP3 and Timeless in lung adenocarcinoma (LUAD). The expression and clinical significance of Timeless were analyzed using the LUAD dataset downloaded from the Cancer Genome Atlas (TCGA). Lentivirus-mediated Timeless knockdown in A549 cells was used to examine the role of Timeless in cell proliferation and pemetrexed (PEM) resistance. Transcription factors (TFs) bound to the Timeless promoter were identified by DNA pull-down technology with HPLC-MS/MS analysis and analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Dual-luciferase reporter assay was used to determine the activity of SP3 in Timeless transcription. Timeless was overexpressed in LUAD samples, and it could serve as a potential diagnostic or prognostic biomarker for LUAD patients. shTimeless-mediated knockdown of Timeless reduced cell viability and proliferation and sensitized PEM-resistant A549 cells to PEM. Four fragments (F1: 1-373 bp), (F2: 374-962 bp), (F4: 1274-1645 bp), and (F5: 1646-2000bp) were confirmed as the TF binding profiles of the Timeless promoter. KEGG analysis showed that the TFs bound to the Timeless promoter had relevance to spliceosome, RNA transport, and mRNA surveillance pathways. SP3 promoted the transcription of Timeless via the F2 fragment (374-962 bp) binding motif. Upregulation of Timeless mediated by SP3 promotes LUAD cell proliferation, providing evidence to support that targeting the SP3/Timeless axis may be a potential therapeutic strategy against LUAD.

Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances.

Nonsense-mediated mRNA decay in eukaryotes is vital to cellular homeostasis. Further knowledge of its putative role in plant RNA metabolism under stress is pivotal to developing fitness-optimizing strategies. Nonsense-mediated mRNA decay (NMD), part of the mRNA surveillance pathway, is an evolutionarily conserved form of gene regulation in all living organisms. Degradation of mRNA-bearing premature termination codons and regulation of physiological RNA levels highlight NMD's role in shaping the cellular transcriptome. Initially regarded as purely a tool for cellular RNA quality control, NMD is now considered to mediate various aspects of plant developmental processes and responses to environmental changes. Here we offer a basic understanding of NMD in eukaryotes by explaining the concept of premature termination codon recognition and NMD complex formation. We also provide a detailed overview of the NMD mechanism and its role in gene regulation. The potential role of effectors, including ABCE1, in ribosome recycling during the translation process is also explained. Recent reports of alternatively spliced variants of corresponding genes targeted by NMD inArabidopsis thalianaare provided in tabular format. Detailed figures are also provided to clarify the NMD concept in plants. In particular, accumulating evidence shows that NMD can serve as a novel alternative strategy for genetic manipulation and can help design RNA-based therapies to combat stress in plants. A key point of emphasis is its function as a gene regulatory mechanism as well as its dynamic regulation by environmental and developmental factors. Overall, a detailed molecular understanding of the NMD mechanism can lead to further diverse applications, such as improving cellular homeostasis in living organisms.

TYROBP as a molecular target in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

Cholangiocarcinoma occurs when there is a malignant tumor in the bile duct system. Renal cancer originates from renal tubular epithelial cells. Abdominal aortic aneurysm (AAA) is a permanently localized dilation caused by a lesion or injury to abdominal aortic wall. However, the relationship between TYROBP and cholangiocarcinoma, renal cancer and AAA remains unclear. The profiles of cholangiocarcinoma dataset GSE107943, renal cell carcinoma dataset GSE213324, and AAA dataset GSE47472 were downloaded from the GEO database using the platforms GPL18573, GPL24676, and GPL10558. DEGs were screened, WGCNA was performed as well as construction and analysis of PPI network. Functional enrichment analysis, GSEA, heat map of gene expression, survival analysis, and immune infiltration analysis were performed. The most relevant diseases to core genes were found by CTD. The GSE107943 dataset identified 3383 DEGs for cholangiocarcinoma, GSE47472 identified 95 DEGs for abdominal aortic aneurysm, and GSE213324 identified 10245 DEGs for renal cell carcinoma. For the GSE107943 cholangiocarcinoma dataset, GO analysis revealed enrichment in immune response, cell adhesion, extracellular space, and oxidoreductase activity. KEGG analysis indicated enrichment in metabolic pathways, the PI3K-Akt signaling pathway, cell apoptosis, the cell cycle, and the NF-kappa B signaling pathway. In the GSE47472 AAA dataset, GO analysis showed enrichment in neuroblast differentiation, cardiac muscle myofilament complex, and alkaline binding. KEGG analysis indicated enrichment in mRNA surveillance pathway and purine metabolism. In the GSE213324 renal cell carcinoma dataset, GO analysis indicated enrichment in immune system processes, cell adhesion, and membrane parts. KEGG analysis showed enrichment in cytokine-cytokine receptor interaction, calcium signaling pathway, and hematopoietic cell lineage. Furthermore, for cholangiocarcinoma (GSE107943), enriched terms associated with DEGs were in metabolic pathways, cell apoptosis, and the cell cycle. For AAA (GSE47472), enriched terms were in alkaline binding and cellular redox homeostasis. For renal cell carcinoma (GSE213324), enriched terms were in biological adhesion, regulation of immune system processes, and cell surface. Common core genes (ADH6, AGXT, CYP3A43, TYROBP) were identified for cholangiocarcinoma, renal cell carcinoma, and AAA. ADH6 and TYROBP were associated with cholangiocarcinoma, AAA, renal tumors, kidney diseases, atherosclerosis, and inflammation. TYROBP is abnormally expressed in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

Comparative Proteomic Analysis Reveals Candidate Pathways Related to the Effect of Different Light Qualities on the Development of Mycelium and Fruiting Body of Pleurotus ostreatus.

Light affects the morphology and physiology of Pleurotus ostreatus. However, the underlying molecular mechanism of this effect remains unclear. In this study, a label-free comparative proteomic analysis was conducted to investigate the global protein expression profile of the mycelia and fruiting bodies of P. ostreatus PH11 growing under four different light quality treatments. Among all the 2234 P. ostreatus proteins, 1349 were quantifiable under all tested conditions. A total of 1100 differentially expressed proteins were identified by comparing the light group data with those of the darkness group. GO and KEGG enrichment analyses indicated that the oxidative phosphorylation, proteasome, and mRNA surveillance pathways were the most related pathways under the light condition. qRT-PCR verified that the expression of the white collar 1 protein was significantly enhanced under white light. Additionally, glutamine synthetase and aldehyde dehydrogenase played important roles during light exposure. This study provides valuable insight into the P. ostreatus light response mechanism, which will lay the foundation for improved cultivation.

Changes in oral, skin, and gut microbiota in children with atopic dermatitis: a case-control study.

Atopic dermatitis (AD) is a common clinical recurrent atopic disease in dermatology, most seen in children and adolescents. In recent years, AD has been found to be closely associated with microbial communities. To explore the synergistic effects between colonizing bacteria from different sites and AD, we comparatively analyzed the skin, oral, and gut microbiota of children with AD (50 individuals) and healthy children (50 individuals) by 16S rRNA gene sequencing. Twenty samples were also randomly selected from both groups for metabolic and macrogenomic sequencing. The results of our sequencing study showed reduced microbiota diversity in the oral, skin, and gut of children with AD (P < 0.05). Metabolomics analysis showed that serotonergic synapse, arachidonic acid metabolism, and steroid biosynthesis were downregulated at all three loci in the oral, skin, and gut of children with AD (P < 0.05). Macrogenomic sequencing analysis showed that KEGG functional pathways of the three site flora were involved in oxidative phosphorylation, ubiquitin-mediated proteolysis, mRNA surveillance pathway, ribosome biogenesis in eukaryotes, proteasome, basal transcription factors, peroxisome, MAPK signaling pathway, mitophagy, fatty acid elongation, and so on (P < 0.05). The combined microbial, metabolic, and macrogenetic analyses identified key bacteria, metabolites, and pathogenic pathways that may be associated with AD development. We provides a more comprehensive and in-depth understanding of the role of the microbiota at different sites in AD patients, pointing to new directions for future diagnosis, treatment and prognosis.

De novo assembly and characterization of the transcriptome of Morchella esculenta growth with selenium supplementation.

Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta. While 5 µg mL-1selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL-1significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL-1 and 10 µg mL-1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.

Role of Sox3 in Estradiol-Induced Sex Reversal in Pelodiscus sinensis.

The Chinese soft-shelled turtle Pelodiscus sinensis, an economically important species in China, exhibits significant sexual dimorphism. Males are more valuable than females owing to their wider calipash and faster growth. Estradiol (E2)-induced sex reversal is used to achieve all-male breeding of turtles; however, the mechanism of this sex reversal remains unclear. In this study, we characterized the Sox3 gene, whose expression level was high in the gonads and brain and exhibited significant sexual dimorphism in the ovary. During embryonic development, Sox3 was highly expressed at the initiation of ovarian differentiation. E2 and Sox3-RNAi treatment before sexual differentiation led to 1352, 908, 990, 1011, and 975 differentially expressed genes in five developmental stages, respectively, compared with only E2 treatment. The differentially expressed genes were clustered into 20 classes. The continuously downregulated and upregulated genes during gonadal differentiation were categorized into Class 0 (n = 271) and Class 19 (n = 606), respectively. KEGG enrichment analysis showed that Sox3 significantly affected sexual differentiation via the Wnt, TGF-β, and TNF signaling pathways and mRNA surveillance pathway. The expression of genes involved in these signaling pathways, such as Dkk4, Nog, Msi1, and Krt14, changed significantly during gonadal differentiation. In conclusion, the deletion of Sox3 may lead to significant upregulation of the mRNA surveillance pathway and TNF and Ras signaling pathways and downregulation of the Wnt and TGF-β signaling pathways, inhibiting E2-induced sex reversal. These findings suggest that Sox3 may play a certain promoting effect during E2-induced sex reversal in P. sinensis.

Persistent exposure to artificial light at night (ALAN) accelerates metamorphosis and colonization in larvae of marine shellfish

The ongoing course of urbanization has led to excessive use of artificial light at night (ALAN), which has rapidly become an important source of pollution in many cities. The Pacific abalone (Haliotis discus hannai) Larvae were kept under a 12/12 h light/dark photoperiod (DD) in order to determine the effects of ALAN on embryonic development. To simulate the street lighting conditions at night, the artificial light was switched on from 18:00 until midnight (AD) or until 06:00 the next day (ND). Moreover, Groups AD and ND had a considerably greater hatching success rate and metamorphosis rate than Group DD (P < 0.05), whereas Group DD had a significantly longer hatching period and course to complete the metamorphosis of the larvae (P < 0.05). Transcriptomic analyses showed that members of Groups AD and DD had considerably higher expression levels of genes involved in ribosome biogenesis, spliceosome function, and the mRNA surveillance pathway. Prostaglandin B2, L-palmitoylcarnitine, stearic acid, palmitic acid, leukotriene C4, and arachidonic acid were screened by non-targeted metabolomics as differential metabolic markers that played a vital role in the response of larvae to different ALAN conditions. Multi-omics correlation analysis suggested that five pathways related to fatty acid synthesis, catabolism, and metabolism, such as biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, were enriched in each comparison. Further quantitative analysis showed that compared to Group DD, 33 out of 50 fatty acids were upregulated in Group AD, and the levels of almost all fatty acids were increased in Group ND, which in turn suggested that fatty acids played a vital role in the physiological response of larvae to illumination changes. The findings of this work were significant for the unbiased and full-scale assessment of the ecological effects of ALAN, as well as the structural stability of the marine benthic community.

Phosphoproteomic landscape of pseudorabies virus infection reveals multiple potential antiviral targets.

Pseudorabies virus (PRV) is a kind of alpha herpesvirus that infects a wide range of animals and even human beings. Therefore, it is important to explore the mechanisms behind PRV replication and pathogenesis. By conducting a tandem mass tag-based phosphoproteome, this study revealed the phosphorylated proteins and cellular response pathways involved in PRV infection. Findings from this study shed light on the relationship between the phosphorylated cellular proteins and PRV infection, as well as guiding the discovery of targets for the development of antiviral compounds against PRV.

SARS-CoV-2 helicase might interfere with cellular nonsense-mediated RNA decay: insights from a bioinformatics study

BackgroundViruses employ diverse strategies to interfere with host defense mechanisms, including the production of proteins that mimic or resemble host proteins. This study aimed to analyze the similarities between SARS-CoV-2 and human proteins, investigate their impact on virus-host interactions, and elucidate underlying mechanisms.ResultsComparing the proteins of SARS-CoV-2 with human and mammalian proteins revealed sequence and structural similarities between viral helicase with human UPF1. The latter is a protein that is involved in nonsense-mediated RNA decay (NMD), an mRNA surveillance pathway which also acts as a cellular defense mechanism against viruses. Protein sequence similarities were also observed between viral nsp3 and human Poly ADP-ribose polymerase (PARP) family of proteins. Gene set enrichment analysis on transcriptomic data derived from SARS-CoV-2 positive samples illustrated the enrichment of genes belonging to the NMD pathway compared with control samples. Moreover, comparing transcriptomic data from SARS-CoV-2-infected samples with transcriptomic data derived from UPF1 knockdown cells demonstrated a significant overlap between datasets.ConclusionsThese findings suggest that helicase/UPF1 sequence and structural similarity might have the ability to interfere with the NMD pathway with pathogenic and immunological implications.