mRNA Surveillance Pathway Research Articles

CircRNA Identification and CircRNA–miRNA–mRNA Network in Cynoglossus semilaevis Sexual Size Dimorphism

Simple SummaryChinese tongue sole (Cynoglossus semilaevis) typically displays female-biased sexual size dimorphism (SSD), but its epigenetic regulatory mechanisms are poorly understood, especially the role of circRNAs. To explore the function of circRNAs in Chinese tongue sole SSD, we firstly identified differentially expressed circular RNAs (DE circRNAs) in female, male, and pseudo-male C. semilaevis. Secondly, the ceRNA network containing DE circRNAs, miRNAs, and mRNAs in the three genders was constructed. Among the ceRNA network, several circRNAs such as novel_circ_004374 and novel_circ_014597 may regulate hipk2 expression by sponging miR-130-x. It is also worth exploring whether or how novel_circ_008696 regulates setd2 by binding to novel-m0387-3p. The present study provided the cirRNA and its ceRNA network that potentially regulate C. semileavis female-biased SSD for the first time. Sexual size dimorphism (SSD), which is the sexual differences in body size, has been widely reported in various species including fishes. For Chinese tongue sole (Cynoglossus semilaevis), a flatfish exhibiting typically female-biased SSD, little is known for its epigenetic regulation mechanism, especially the role of circRNAs. Here, we identified the differently expressed abundances of circRNAs in females, males, and pseudo-males to explore the potential functions of circRNAs in Chinese tongue sole SSD. In total, 14,745 novel circRNAs were screened, among which 1461 DE circRNAs were identified from the brain, gonad, liver, and muscle in female, male, and pseudo-male individuals. The ceRNA network was subsequently constructed, including 10 circRNAs, 26 mRNAs, and 11 miRNAs. These DE mRNAs were mainly related to the mRNA surveillance pathway, metabolic pathways, and cellular senescence. Importantly, the ceRNA network has revealed that several circRNAs such as novel_circ_004374 and novel_circ_014597 may regulate homeodomain interacting protein kinase 2 (hipk2) expression by sponging miR-130-x. It is also worth exploring whether or how novel_circ_008696 regulates SET Domain Containing 2, histone lysine methyltransferase (setd2), which in turn affects the epigenetic patterns of different sexual individuals. The present study not only enriches the knowledge on the potential roles of circRNA in the physiological process, but also provides new clues for the explanation of fish SSD. In future studies, the precise function and involvement of circRNAs in female-biased SSD will require more efforts.

Identification of gonadal associated genes in black tiger shrimp ( Penaeus monodon ) using transcriptome analysis and high‐throughput sequencing

Black tiger shrimp (Penaeus monodon) is a commercially important species. It is reported to have low reproductive maturation rates in captivity. To improve the production of this species via sustainable aquaculture, genetic techniques are required to improve its maturation rates. However, to date, reports on P. monodon reproduction at a transcriptional level are limited. To address this, we conducted transcriptome sequencing of the ovaries and testes of P. monodon using high-throughput sequencing to identify sex-related pathways and genes. A total of 75.74 Gb of clean data were generated from nine gonadal tissue libraries. We obtained 62,276 unigenes with a mean length of 1452 bp and N50 of 2423 bp. A total of 11,411 significantly differentially expressed genes (DEGs) were identified between the testis and developed ovaries. Enrichment analysis of the DEGs identified 415 significantly enriched GO terms and 106 enriched KEGG pathways. Genes related to the P. monodon ovaries were enriched in the steroid biosynthesis, mRNA surveillance, nucleocytoplasmic transport, oxidative phosphorylation and DNA replication pathways. Five upregulated and five downregulated ovarian genes were confirmed using RT-PCR. This investigation has thus identified important sex-related functional genes, GO terms and pathways in P. monodon. In particular, we identified several important genes and pathways related to gonadal development, such as GnRH/GnRHR-like, Hsp90, PCNA, cathepsin L, Wnt signalling pathway and ovarian steroidogenesis pathway, which provide important insights into the mechanism analysis and sex regulation of shrimp gonadal development. The results will provide reference data for future research into the reproductive biology of shrimp, which will aid in improved black tiger shrimp breeding in captivity.

Expression and Prognostic Value of Chromobox Family Proteins in Esophageal Cancer.

Background: Esophageal cancer (EC) is one of the most common human malignant tumors worldwide. Chromobox (CBX) family proteins are significant components of epigenetic regulatory complexes. It is reported that CBXs play critical roles in the oncogenesis and development of various tumors. Nonetheless, their functions and specific roles in EC remain vague and obscure. Methods and Materials: We used multiple bioinformatics tools, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), UALCAN, Kaplan–Meier plotter, cBioPortal, Metascape, TIMER2 and TISIDB, to investigate the expression profile, gene alterations and prognostic roles of CBX family proteins, as well as their association with clinicopathologic parameters, immune cells and immune regulators. In addition, RT-qPCR, Western blot, CCK8, colony formation, wound healing and transwell assays were performed to investigate the biological functions of CBX3 in EC cells. Results: CBX3 and CBX5 were overexpressed in EC compared to normal tissues. Survival analysis revealed that high expression of CBX1 predicted worse disease-free survival (DFS) in EC patients. Functionally, CBXs might participate in mismatch repair, spliceosome, cell cycle, the Fanconi anemia pathway, tight junction, the mRNA surveillance pathway and the Hippo signaling pathway in EC development. Furthermore, CBXs were related to distinct immune cells infiltration and immune regulators. Additionally, depletion of CBX3 inhibited the proliferation, migration and invasion abilities of EC cells. Conclusions: Our study comprehensively investigated the expression pattern, prognostic value, and gene alterations of CBXs in EC, as well as their relationships with clinicopathologic variables, immune cells infiltration and immune regulators. These results suggested that CBX family proteins, especially CBX3, might be potential biomarkers in the progression of EC.

Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis.

Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis. By genome/exome sequencing, we found recessive variants in FOCAD segregating with the disease. Zebrafish lacking focad phenocopied the human disease, revealing a signature of altered messenger RNA (mRNA) degradation processes in the liver. Using patient's primary cells and CRISPR-Cas9-mediated inactivation in human hepatic cell lines, we found that FOCAD deficiency compromises the SKI mRNA surveillance pathway by reducing the levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes exhibited lowered albumin expression and signs of persistent injury accompanied by CCL2 overproduction. Our results reveal the importance of FOCAD in maintaining liver homeostasis and disclose a possible therapeutic intervention point via inhibition of the CCL2/CCR2 signaling axis.

Correlation Between the RNA Methylation Genes and Immune Infiltration and Prognosis of Patients with Hepatocellular Carcinoma: A Pan-Cancer Analysis.

BackgroundRNA methylation is one of the most common RNA modifications and is dynamic and reversible. The enzymes and downstream effectors associated with RNA methylation modifications can be targeted to regulate RNA methylation levels. This mechanism can affect RNA processing, metabolism, cell proliferation and migration, and regulation of physiological or pathological processes. The aim of this study was to investigate the role of RNA methylation-related genes in hepatocellular carcinoma (HCC).MethodsBaseline RNA methylation data were extracted from The Cancer Genome Atlas database. The expression pattern, predictive value, mutational profile, and interaction network of RNA methylation genes in pancancer were examined. Then, the association between the expression of RNA methylation genes and immune infiltration was investigated. In addition, a risk score model for HCC was developed and analyzed.ResultsCancer cells had a higher expression of RNA methylation genes than normal cells in some cancer cells, and a higher expression of RNA methylation genes could negatively affect patient prognosis. Enrichment analysis revealed that RNA methylation genes are involved in the mRNA surveillance pathway and RNA degradation and transport. A 4-gene (ALYREF, NSUN4, TRMT6, YTHDF1) prognostic signature was established to predict HCC prognosis based on RNA methylation-related genes. Finally, the role of prognostic models in HCC was validated.ConclusionRNA methylation genes can be an indicator of oncogenicity in relation to HCC prognosis and are associated with immune infiltration in the tumour microenvironment. This finding could provide clinicians with the opportunity to explore new strategic approaches.

Chromatin accessibility of Meyerozyma guilliermondii under patulin stress

Patulin (PAT) is a significant mycotoxin contaminant in apples and their product. Antagonist yeasts can inhibit PAT production or degrade PAT in vivo or in vitro. Our previous study reported that Meyerozyma guilliermondii, an antagonistic yeast, could degrade PAT. The present study aims to explore the molecular mechanisms of M. guilliermondii in response to PAT stress by chromatin accessibility sequencing. After PAT treatment, four genes were up-regulated, and 146 were down-regulated in M. guilliermondii. Gene Ontology (GO) analysis showed that differential expression of genes related to yeast growth, stimulus-response, and activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that PAT stress caused toxic damage to the yeast by affecting the functions such as steroid biosynthesis, ATP-binding cassette (ABC) transporters, autophagy-yeast, messenger RNA (mRNA) surveillance pathways, mitogen activated protein kinase (MAPK) signaling pathway and protein processing in the endoplasmic reticulum. Gene function analysis showed that multidrug resistance protein encoding gene (MDR1), heat shock protein 70 kDa encoding gene (SSC1) and 14-3-3 protein encoding gene (BMH1) might participate in the detoxification of PAT by M. guilliermondii through the stress response. In addition, these three genes might be regulated by the yeast activator protein (YAP) sub-family. In short, the information obtained in this study reveals the regulatory role of related transcription factors in M. guilliermondii responding to PAT stress.

Regulating Strategies of Transcription and Alternative Splicing for Cold Tolerance Harpadon nehereus Fish

In recent years, Harpadon nehereus gradually become a dominant species with great potential for exploitation in the East China Sea, and it is worth investigating whether H. nehereus would tolerate cold stress to continue to expand into the colder northern waters. The molecular regulation level is favorable evidence to explore the cold tolerance of H. nehereus, a total of 6,650, 1,936, and 2,772 differentially expressed genes (DEGs) in transcription regulation, and 4,409, 1,250, and 2,303 differential alternative splicing genes (DASGs) in alternative splicing regulation were identified in H. nehereus at 13, 15, and 17°C, respectively, importantly, 47 genes were identified as the key candidate genes for cold tolerance in H. nehereus. In transcription regulation, up-regulated DEGs were enriched in metabolic process terms and ribosome, spliceosome pathway, etc., while down-regulated DEGs were enriched in signal transduction terms, focal adhesion, proteoglycans in cancer pathway, etc., at 13, 15, and 17°C, respectively. In alternative splicing regulation, spliceosome, mRNA surveillance pathway, etc., were significantly enriched in DASGs. In a word, H. nehereus adapts to cold environments mainly through transcription and translation, transmembrane transport, protein modification, etc., while cold stress may also induce some diseases in H. nehereus.

Impact of Environmentally Relevant Concentrations of Bisphenol A (BPA) on the Gene Expression Profile in an In Vitro Model of the Normal Human Ovary.

Endocrine-disrupting chemicals (EDCs), including the xenoestrogen Bisphenol A (BPA), can interfere with hormonal signalling. Despite increasing reports of adverse health effects associated with exposure to EDCs, there are limited data on the effect of BPA in normal human ovaries. In this paper, we present a detailed analysis of the transcriptomic landscape in normal Human Epithelial Ovarian Cells (HOSEpiC) treated with BPA (10 and 100 nM). Gene expression profiles were determined using high-throughput RNA sequencing, followed by functional analyses using bioinformatics tools. In total, 272 and 454 differentially expressed genes (DEGs) were identified in 10 and 100 nM BPA-treated HOSEpiCs, respectively, compared to untreated controls. Biological pathways included mRNA surveillance pathways, oocyte meiosis, cellular senescence, and transcriptional misregulation in cancer. BPA exposure has a considerable impact on 10 genes: ANAPC2, AURKA, CDK1, CCNA2, CCNB1, PLK1, BUB1, KIF22, PDE3B, and CCNB3, which are also associated with progesterone-mediated oocyte maturation pathways. Future studies should further explore the effects of BPA and its metabolites in the ovaries in health and disease, making use of validated in vitro and in vivo models to generate data that will address existing knowledge gaps in basic biology, hazard characterisation, and risk assessment associated with the use of xenoestrogens such as BPA.

UPF1 promotes rapid degradation of m6A-containing RNAs

N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNAs and affects RNA processing and metabolism. When YTHDF2, an m6A-recognizing protein, binds to m6A, it facilitates the destabilization of m6A-containing RNAs (m6A RNAs). Here, we demonstrate that upstream frameshift 1 (UPF1), a key factor for nonsense-mediated mRNA decay, interacts with YTHDF2, thereby triggering rapid degradation of m6A RNAs. The UPF1-mediated m6A RNA degradation depends on a specific interaction between UPF1 and N-terminal residues 101-168 of YTHDF2, UPF1 ATPase/helicase activities, and UPF1 interaction with proline-rich nuclear receptor coactivator 2 (PNRC2), a decapping-promoting factor preferentially involved in nonsense-mediated mRNA decay. Furthermore, transcriptome-wide analyses show that YTHDF2-bound mRNAs that are not substrates for HRSP12-RNase P/MRP-mediated endoribonucleolytic cleavage are destabilized with a higher dependency on UPF1. Collectively, our data indicate dynamic and multilayered regulation of the stability of m6A RNAs and highlight the multifaceted role of UPF1 in mRNA decay.

Transcriptomics Integrated with Changes in Cell Wall Material of Chestnut (Castanea mollissima Blume) during Storage Provides a New Insight into the "Calcification" Process.

Chestnut “calcification” is the result of a series of physiological and biochemical changes during postharvest storage; however, the associated mechanisms are unclear. In this study, several potential calcification-related physicochemical parameters in chestnut, including moisture, cell wall materials, cellulose, lignin, and pectin, were measured. Transcriptome analysis was performed on chestnut seeds during different stages of storage. The results showed that the degree of calcification in the chestnut seeds was significantly negatively correlated with the moisture content (r = −0.961) at room temperature (20–25 °C) and a relative humidity of 50–60%. The accumulation of cell wall material in completely calcified seeds was 5.3 times higher than that of fresh seeds. The total content of cellulose and lignin increased during the storage process. Transcriptome analysis of 0% and 50% calcified chestnut was performed; a total of 1801 differentially expressed genes consisting of 805 up-regulated and 996 down-regulated genes were identified during the calcification process. Furthermore, response to water, water deprivation, and salt stress were most enriched by gene ontology (GO) and gene set enrichment analysis (GSEA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to chestnut calcification included purine metabolism, RNA degradation, the mRNA surveillance pathway, starch and sucrose metabolism, arginine and proline metabolism, and fatty acid metabolism, and were detected. Most of the genes involved in cellulose synthase, lignin catabolism, and pectin catabolism were down-regulated, while only two important genes, scaffold11300 and scaffold0412, were up-regulated, which were annotated as cellulose and pectin synthase genes, respectively. These two genes may contribute to the increase of total cell wall material accumulation during chestnut calcification. The results provided new insights into chestnut calcification process and laid a foundation for further chestnut preservation.

Establishment of DNA Methylation Profile Associated with TCM Syndrome in Endometriosis.

Objectives To screen the potential epigenetic biomarkers associated with endometriosis (EMS) and traditional Chinese medicine (TCM) syndrome EMS types. Methods A cohort of 99 participants comprising 42 EMS patients with cold coagulation blood stasis (CCBS) syndrome, 35 EMS patients with Qi stagnation blood stasis (QSBS) syndrome, and 22 women of childbearing age without EMS were recruited. Reduced representation bisulfite sequencing (RRBS) was used to establish the differential DNA methylation profiles in human peripheral blood samples obtained from four non-EMS and four EMS patients with CCBS or QSBS syndrome, respectively. Differentially expressed genes (DEGs) were verified in 18 non-EMS, 38 CCBS-EMS, and 31 QSBS-EMS using pyrosequencing. Results Methylation sites of 123942, 127229, and 115961 were found in peripheral blood DNA of non-EMS, CCBS-EMS, and QSBS-EMS patients, respectively. GO and KEGG analyses showed that the pathological process of EMS may be closely related to the nervous system development, cell junctions, GABA-gated chloride ion channel activity, nicotine addiction, Hippo signaling pathway, mRNA surveillance pathway, and Wnt signaling pathway. The methylation level at CpG site within HDAC6 gene in QSBS-EMS patients was significantly different from that in control women. Conclusions The changes in DNA methylation in peripheral blood samples may be associated with EMS and TCM syndrome EMS types. The methylation level of HDAC6 gene may be used to distinguish QSBS-EMS patients from women without EMS.

Osteoarticular Involvement-Associated Biomarkers and Pathways in Psoriasis: The Shared Pathway With Ankylosing Spondylitis.

Psoriatic arthritis (PsA) is a unique immune-mediated disease with cutaneous and osteoarticular involvement. However, only a few studies have explored the susceptibility of osteoarticular involvement in psoriasis (Ps) at the genetic level. This study investigated the biomarkers associated with osteoarticular participation and potential shared molecular mechanisms for PsA and ankylosing spondylitis (AS).MethodsThe RNA-seq data of Ps, PsA, and AS in the Gene Expression Omnibus (GEO) database were obtained. First, we used the limma package and the weighted gene co-expression network analysis (WGCNA) to identify the potential genes related to PsA and AS. Then, the shared genes in PsA and AS were performed using the GO, KEGG, and GSEA analyses. We also used machine learning to screen hub genes. The results were validated using external datasets and native cohorts. Finally, we used the CIBERSORT algorithm to estimate the correlation between hub genes and the abundance of immune cells in tissues.ResultsAn overlap was observed between the PsA and AS-related modules as 9 genes. For differentially expressed genes in AS and PsA, only one overlapping gene was found (COX7B). Gene enrichment analysis showed that the above 9 genes might be related to the mRNA surveillance pathway. The GSEA analyses showed that COX7B was involved in adaptive immune response, cell activation, etc. The PUM1 and ZFP91, identified from the support vector machine, had preferable values as diagnostic markers for osteoarticular involvement in Ps and AS (AUC > 0.7). Finally, CIBERSORT results showed PUM1 and ZFP91 involvement in changes of the immune microenvironment.ConclusionFor the first time, this study showed that the osteoarticular involvement in psoriasis and AS could be mediated by the mRNA surveillance pathway-mediated abnormal immunologic process. The biological processes may represent the cross talk between PsA and AS. Therefore, PUM1 and ZFP91 could be used as potential biomarkers or therapeutic targets for AS and Ps patients.

New Insights Into PTBP3 in Human Cancers: Immune Cell Infiltration, TMB, MSI, PDCD1 and m6A Markers.

Polypyrimidine tract binding protein 3 (PTBP3) plays a critical role in post-transcriptional regulation. The role of PTBP3 in various human tumours was explored and analysed in this study based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PTBP3 was highly expressed in most tumours, such as breast invasive carcinoma, colon adenocarcinoma and hepatocellular carcinoma. PTBP3 overexpression generally predicts poor overall survival and disease-free survival in patients with adrenocortical carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. However, low PTBP3 expression predicts poor prognosis in kidney renal clear cell carcinoma. We also explored PTBP3 genetic alterations in different tumour tissues. The result found that the frequency of PTBP3 alteration (>4%) was the highest in uterine tumours with “mutation” as the primary type. Furthermore, we found a significant correlation between PTBP3 expression and tumour mutational burden and microsatellite instability in various human tumours, and found that PTBP3 expression was positively correlated with TMB in ACC, STAD, PAAD, LUAD, and SARC. Two enhanced phosphorylation levels of S30 and S426 in colon cancer, ovarian cancer, and uterine corpus endometrial carcinoma were found. Further analysis indicated that PTBP3 expression was positively correlated with the cancer-associated fibroblasts for most tumour types. This study also found a relationship between immune checkpoints and N6-methyladenosine-related markers and PTBP3 expression. Moreover, the “mRNA surveillance pathway” and “RNA degradation” were involved in the functional mechanisms of PTBP3. These results provide new insights for molecular studies, and integrative analysis provided a framework for determining the predictive, prognostic, and therapeutic relevance of PTBP3 in cancer patients.

Analysis of mRNA-derived siRNAs in mutants of mRNA maturation and surveillance pathways in Arabidopsis thaliana

Defects in RNA maturation and RNA decay factors may generate substrates for the RNA interference machinery. This phenomenon was observed in plants where mutations in some RNA-related factors lead to the production of RNA-quality control small interfering RNAs and several mutants show enhanced silencing of reporter transgenes. To assess the potential of RNAi activation on endogenous transcripts, we sequenced small RNAs from a set of Arabidopsis thaliana mutants with defects in various RNA metabolism pathways. We observed a global production of siRNAs caused by inefficient pre-mRNA cleavage and polyadenylation leading to read-through transcription into downstream antisense genes. In addition, in the lsm1a lsm1b double mutant, we identified NIA1, SMXL5, and several miRNA-targeted mRNAs as producing siRNAs, a group of transcripts suggested being especially sensitive to deficiencies in RNA metabolism. However, in most cases, RNA metabolism perturbations do not lead to the widespread production of siRNA derived from mRNA molecules. This observation is contrary to multiple studies based on reporter transgenes and suggests that only a very high accumulation of defective mRNA species caused by specific mutations or substantial RNA processing defects trigger RNAi pathways.

De novo Transcriptome Analysis in Leymus mollis to Unveil Genes Involved in Salt Stress Response

Leymus mollis, a wild relative of wheat, is very tolerant to salt stress, and has been considered as a valuable genetic resource for wheat breeding. However, the genetic basis for salt tolerance of this species is still largely unknown. In this study, de novo sequencing, assembly and analysis of L. mollis transcriptome in response to salt stress was performed. A total of 110,323 and 112,846 unigenes were generated for the NaCl-free (CK) and 180 mM NaCl-treated (CT) library, respectively. For the two libraries, 73,414 unigenes were successfully annotated in five common protein databases, and 7521 differentially expressed genes (DEGs) between CK and CT libraries were identified. GO enrichment analysis of the DEGs showed that the significantly enriched GO terms were predominantly involved in environmental adaptation (including “response to abiotic stimulus”, “response to water deprivation”), regulation of signaling pathway (such as “regulation of abscisic acid mediated signaling pathway”, “regulation of cell communication”), and photosynthesis (including “response to light stimulus”, “photosynthesis, light harvesting” and “chlorophyll metabolic process”). KEGG pathway enrichment analysis showed that “mRNA surveillance pathway”, “RNA transport” and “plant hormone signal transduction” were predominantly enriched pathways, followed by several secondary metabolic pathways, photosynthesis, carbohydrate metabolism and lipid metabolism. In addition, DEGs related to osmotic stress, ion homeostasis and oxidative stress, including four dehydrins, five aquaporins, an LmNHX2 and several antioxidant enzymes or proteins genes, were found to be up-regulated in response to salt stress. These results will be helpful for further studies on the molecular mechanisms of salt responses in L. mollis.

The cap-snatching frequency of a plant bunyavirus from nonsense mRNAs is low but is increased by silencing of UPF1 or SMG7.

Bunyaviruses cleave host cellular mRNAs to acquire cap structures for their own mRNAs in a process called cap‐snatching. How bunyaviruses interact with cellular mRNA surveillance pathways such as nonsense‐mediated decay (NMD) during cap‐snatching remains poorly understood, especially in plants. Rice stripe virus (RSV) is a plant bunyavirus threatening rice production in East Asia. Here, with a newly developed system allowing us to present defined mRNAs to RSV in Nicotiana benthamiana, we found that the frequency of RSV to target nonsense mRNAs (nsRNAs) during cap‐snatching was much lower than its frequency to target normal mRNAs. The frequency of RSV to target nsRNAs was increased by virus‐induced gene silencing of UPF1 or SMG7, each encoding a protein component involved in early steps of NMD (in an rdr6 RNAi background). Coincidently, RSV accumulation was increased in the UPF1‐ or SMG7‐silenced plants. These data indicated that the frequency of RSV to target nsRNAs during cap‐snatching is restricted by NMD. By restricting the frequency of RSV to target nsRNAs, NMD may impose a constraint to the overall cap‐snatching efficiency of RSV. Besides a deeper understanding for the cap‐snatching of RSV, these findings point to a novel role of NMD in plant–bunyavirus interactions.

Dynamics of Known Long Non-Coding RNAs during the Maternal-to-Zygotic Transition in Rabbit.

Simple SummaryWe first revealed the expression profile of rabbit known lncRNAs during embryo pre-implantation development and showed minor and major wave of zygotic lncRNAs synthesis. The study then selected the differentially expressed (DE) lncRNAs between consecutive stages and predicted their potential target genes. The GO and KEGG analyses suggested that the lncRNAs participate in the regulation of embryo cleavage and development. Additionally, the sequential degradation of maternal lncRNAs showed that, like maternal mRNAs, maternal lncRNAs degradation occurred via maternal and zygotic pathways and the late-degraded lncRNAs might play a role in the degradation of mRNAs through mRNA surveillance pathway.The control of pre-implantation development in mammals undergoes a maternal-to-zygotic transition (MZT) after fertilization. The transition involves maternal clearance and zygotic genome activation remodeling the terminal differentiated gamete to confer totipotency. In the study, we first determined the profile of long non-coding RNAs (lncRNAs) of mature rabbit oocyte, 2-cell, 4-cell, 8-cell, and morula embryos using RNA-seq. A total of 2673 known rabbit lncRNAs were identified. The lncRNAs exhibited dynamic expression patterns during pre-implantation development. Moreover, 107 differentially expressed lncRNAs (DE lncRNAs) were detected between mature oocyte and 2-cell embryo, while 419 DE lncRNAs were detected between 8-cell embryo and morula, consistent with the occurrence of minor and major zygotic genome activation (ZGA) wave of rabbit pre-implanted embryo. This study then predicted the potential target genes of DE lncRNAs based on the trans-regulation mechanism of lncRNAs. The GO and KEGG analyses showed that lncRNAs with stage-specific expression patterns promoted embryo cleavage and synchronic development by regulating gene transcription and translation, intracellular metabolism and organelle organization, and intercellular signaling transduction. The correlation analysis between mRNAs and lncRNAs identified that lncRNAs ENSOCUG00000034943 and ENSOCUG00000036338 may play a vital role in the late-period pre-implantation development by regulating ILF2 gene. This study also found that the sequential degradation of maternal lncRNAs occurred through maternal and zygotic pathways. Furthermore, the function analysis of the late-degraded lncRNAs suggested that these lncRNAs may play a role in the mRNA degradation in embryos via mRNA surveillance pathway. Therefore, this work provides a global view of known lncRNAs in rabbit pre-implantation development and highlights the role of lncRNAs in embryogenesis regulation.

Genes involved in mRNA surveillance are induced in Brachypodium distachyon under cadmium toxicity.

Cd accumulation in plant cells results in dramatic problems including oxidative stress and inhibition of vital enzymes. It also affects mineral uptakes by disrupting membrane permeability. Interaction among Cd and other plant nutrient elements changes the nutritional contents of crops and reduces their yield. In the present study, Cd stress in Brachypodium distachyon led to the upregulation of some heavy metal transport genes (influx or efflux) encoding cation-efflux proteins, heavy metal-associated proteins and NRAMP proteins. The Arabidopsis orthologs of the differentially expressed B. distachyon genes (DEGs) under Cd toxicity were identified, which exhibited Bradi4g26905 was an ortholog of AtALY1-2. Detailed co-expression network and gene ontology analyses found the potential involvement of the mRNA surveillance pathway in Cd tolerance in B. distachyon. These genes were shown to be downregulated by sulfur (S) deficiency. This is the first transcriptomic study investigating the effect of Cd toxicity in B. distachyon, a model plant for genomic studies in Poaceae (Gramineae) species. The results are expected to provide valuable information for more comprehensive research related to heavy metal toxicity in plants.

YTHDF2 is a Potential Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC or KIRC) has a high mortality rate globally. It is necessary to identify biomarkers and investigate the mechanisms those biomarkers are associated with, to improve the prognosis of patients with KIRC. N6-Methyladenosine (m6A) affects the fate of modified RNA molecules and is involved in tumor progression. Different webservers were used in our research to investigate the mRNA transcription and clinical significance of YTHDF2 in KIRC. Survival analysis revealed that patients with elevated YTHDF2 transcription had a slightly longer OS and DFS than those with low YTHDF2 expression. YTHDF2 expression was shown to be significantly associated with the abundance of immune cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. For a series of enrichment studies, we combined information on YTHDF2-binding molecules and expression-linked genes and identified the possible influence of “mRNA surveillance pathway,” “RNA degradation,” and “RNA transport” in the biology or pathogeny of KIRC. In addition, we identified multiple miRNA, kinase, and transcription factor targets of YTHDF2 in KIRC and constructed target networks. Overall, our findings show that YTHDF2 is a possible indicator of immune infiltration in the KIRC.

UPF1: From mRNA Surveillance to Protein Quality Control.

Selective recognition and removal of faulty transcripts and misfolded polypeptides are crucial for cell viability. In eukaryotic cells, nonsense-mediated mRNA decay (NMD) constitutes an mRNA surveillance pathway for sensing and degrading aberrant transcripts harboring premature termination codons (PTCs). NMD functions also as a post-transcriptional gene regulatory mechanism by downregulating naturally occurring mRNAs. As NMD is activated only after a ribosome reaches a PTC, PTC-containing mRNAs inevitably produce truncated and potentially misfolded polypeptides as byproducts. To cope with the emergence of misfolded polypeptides, eukaryotic cells have evolved sophisticated mechanisms such as chaperone-mediated protein refolding, rapid degradation of misfolded polypeptides through the ubiquitin–proteasome system, and sequestration of misfolded polypeptides to the aggresome for autophagy-mediated degradation. In this review, we discuss how UPF1, a key NMD factor, contributes to the selective removal of faulty transcripts via NMD at the molecular level. We then highlight recent advances on UPF1-mediated communication between mRNA surveillance and protein quality control.