RNA BiologyPub Date : 2025-12-01Epub Date: 2025-03-02DOI: 10.1080/15476286.2025.2472448
Nils Peiter, Anna Einert, Pauline Just, Frida Jannasch, Marija Najdovska, Michael Rother
{"title":"Defining the methanogenic SECIS element <i>in vivo</i> by targeted mutagenesis.","authors":"Nils Peiter, Anna Einert, Pauline Just, Frida Jannasch, Marija Najdovska, Michael Rother","doi":"10.1080/15476286.2025.2472448","DOIUrl":"10.1080/15476286.2025.2472448","url":null,"abstract":"<p><p>In all domains of life, Archaea, Eukarya and Bacteria, the unusual amino acid selenocysteine (Sec) is co-translationally incorporated into proteins by recoding a UGA stop codon to a sense codon. A secondary structure on the mRNA, the selenocysteine insertion sequence (SECIS), is required, but its position, secondary structure and binding partner(s) are not conserved across the tree of life. Thus far, the nature of archaeal SECIS elements has been derived mainly from sequence analyses. A recently developed <i>in vivo</i> reporter system was used to study the structure-function relationships of SECIS elements in <i>Methanococcus maripaludis</i>. Through targeted mutagenesis, we defined the minimal functional SECIS element, the parts of the SECIS where structure and not the identity of the bases are relevant for function, and identified two conserved -and invariant- adenines that are most likely to interact with the other factor(s) of the Sec recoding machinery. Finally, we demonstrated the functionality of SECIS elements in the 5`-untranslated region of the mRNA and identified a potential mechanism of SECIS repositioning in the vicinity of the UGA for efficient selenocysteine insertion.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2025-12-01Epub Date: 2025-01-20DOI: 10.1080/21505594.2025.2453818
Su Hyun Park, Yun Hye Kim, Hyeon Jin Lee, Jeong Moo Han, Byoung-Joo Seo, Gyeong-Seo Park, Chonghan Kim, Young Bae Ryu, Woo Sik Kim
{"title":"Immunogenicity and vaccine efficacy of <i>Actinobacillus pleuropneumoniae</i>-derived extracellular vesicles as a novel vaccine candidate.","authors":"Su Hyun Park, Yun Hye Kim, Hyeon Jin Lee, Jeong Moo Han, Byoung-Joo Seo, Gyeong-Seo Park, Chonghan Kim, Young Bae Ryu, Woo Sik Kim","doi":"10.1080/21505594.2025.2453818","DOIUrl":"10.1080/21505594.2025.2453818","url":null,"abstract":"<p><p><i>Actinobacillus pleuropneumoniae</i> (APP) is a significant pathogen in the swine industry, leading to substantial economic losses and highlighting the need for effective vaccines. This study evaluates the potential of APP-derived extracellular vesicles (APP-EVs) as a vaccine candidate compared to the commercial Coglapix vaccine. APP-EVs, isolated using tangential flow filtration (TFF) and cushioned ultracentrifugation, exhibited an average size of 105 nm and a zeta potential of -17.4 mV. These EVs demonstrated stability under external stressors, such as pH changes and enzymatic exposure and were found to contain 86 major metabolites. Additionally, APP-EVs induced dendritic cell (DC) maturation in a Toll-like receptor 4 (TLR4)-dependent manner without cytotoxicity. APP-EVs predominantly elicited Th1-mediated IgG responses in immunized mice without significant liver and kidney toxicity. Contrarily, unlike Coglapix, which induced stronger Th2-mediated responses and notable toxicity. In addition, APP-EVs triggered APP-specific Th1, Th17, and cytotoxic T lymphocyte (CTL) responses and promoted the activation of multifunctional T-cells. Notably, APP-EV immunization enhanced macrophage phagocytosis and improved survival rates in mice challenged with APP infection compared to those treated with Coglapix. These findings suggest that APP-EVs are promising vaccine candidates, capable of inducing potent APP-specific T-cell responses, particularly Th1, Th17, CTL, and multifunctional T-cells, thereby enhancing the protective immune response against APP infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2453818"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-02-20DOI: 10.1080/15592294.2025.2469205
Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith
{"title":"Poly-epigenetic scores for cardiometabolic risk factors interact with demographic factors and health behaviors in older US Adults.","authors":"Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith","doi":"10.1080/15592294.2025.2469205","DOIUrl":"10.1080/15592294.2025.2469205","url":null,"abstract":"<p><p>Poly-epigenetic scores (PEGS) are surrogate measures that help capture individual-level risk. Understanding how the associations between PEGS and cardiometabolic risk factors vary by demographics and health behaviors is crucial for lowering the burden of cardiometabolic diseases. We used results from established epigenome-wide association studies to construct trait-specific PEGS from whole blood DNA methylation for systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), C-reactive protein (CRP), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglycerides (TG), and fasting glucose. Overall and race-stratified associations between PEGS and corresponding traits were examined in adults >50 years from the Health and Retirement Study (<i>n</i> = 3,996, mean age = 79.5 years). We investigated how demographics (age, sex, educational attainment) and health behaviors (smoking, alcohol consumption, physical activity) modified these associations. All PEGS were positively associated with their corresponding cardiometabolic traits (<i>p</i> < 0.05), and most associations persisted across all racial/ethnic groups. Associations for BMI, HDL-C, and TG were stronger in younger participants, and BMI and HDL-C associations were stronger in females. The CRP association was stronger among those with a high school degree. Finally, the HDL-C association was stronger among current smokers. These findings support PEGS as robust surrogate measures and suggest the associations may differ among subgroups.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2469205"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coupling mechanisms coordinating mRNA translation with stages of the mRNA lifecycle.","authors":"Valeria Famà, Lucia Coscujuela Tarrero, Roberto Albanese, Lorenzo Calviello, Stefano Biffo, Mattia Pelizzola, Mattia Furlan","doi":"10.1080/15476286.2025.2483001","DOIUrl":"10.1080/15476286.2025.2483001","url":null,"abstract":"<p><p>Gene expression involves a series of consequential processes, beginning with mRNA synthesis and culminating in translation. Traditionally studied as a linear sequence of events, recent findings challenge this perspective, revealing coupling mechanisms that coordinate key steps of gene expression, even when spatially and temporally distant. In this review, we focus on translation, the final stage of gene expression, and examine its coupling with key stages of mRNA metabolism: synthesis, processing, export, and decay. For each of these processes, we provide an overview of known instances of coupling with translation. Furthermore, we discuss the role of high-throughput technologies in uncovering these intricate interactions on a genome-wide scale. Finally, we highlight key challenges and propose future directions to advance our understanding of how coupling mechanisms orchestrate robust and adaptable gene expression programs.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2025-12-01Epub Date: 2025-03-06DOI: 10.1080/21505594.2025.2474866
Wei Peng, Qinggen Jiang, Yuting Wu, Li He, Bei Li, Weicheng Bei, Xia Yang
{"title":"The role of glutathione for oxidative stress and pathogenicity of <i>Streptococcus suis</i>.","authors":"Wei Peng, Qinggen Jiang, Yuting Wu, Li He, Bei Li, Weicheng Bei, Xia Yang","doi":"10.1080/21505594.2025.2474866","DOIUrl":"10.1080/21505594.2025.2474866","url":null,"abstract":"<p><p><i>Streptococcus suis</i> is an important zoonotic pathogen that threatens human and pig health. During infection, the host can impose oxidative stress to resist pathogen invasion. Resistance to oxidative toxicity is an important factor for pathogens. Glutathione synthesis contributes to reactive oxygen species (ROS) detoxification in bacterial cells. Little is known about the roles of glutathione synthesis and transport in <i>S</i>. <i>suis</i>. In this study, we demonstrated that glutathione treatment increased oxidative stress tolerance in <i>S</i>. <i>suis</i>. GshAB and GshT were found in <i>S</i>. <i>suis</i> glutathione synthesis and import by bioinformatics. In vitro, inactivation of <i>gshAB</i> and <i>gshT</i> led to increased sensitivity to oxidative stress. Inactivation of <i>gshT</i> led to growth defects in the medium. The intracellular glutathione content of <i>gshAB</i> or <i>gshT</i> deletion mutants was lower than that of wild type (WT) strain. The phagocytic resistance of <i>gshAB</i> and <i>gshT</i> mutants was lower than that of the WT strain. Moreover, the virulence of <i>gshAB</i> and <i>gshT</i> deletion mutants was significantly lower than that of the WT strain in mouse survival and tissue loading experiments. In conclusion, these results revealed the functions of GshAB and GshT in the pathogenesis of <i>S. suis</i>. These findings enhance our understanding of bacterial virulence mechanisms and may provide a new avenue for therapeutic intervention aimed at curbing <i>S. suis</i> infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2474866"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-04-29DOI: 10.1080/15476286.2025.2498203
Rita Pancsa, Dmitry E Andreev, Kellie Dean
{"title":"The implication of non-AUG-initiated N-terminally extended proteoforms in cancer.","authors":"Rita Pancsa, Dmitry E Andreev, Kellie Dean","doi":"10.1080/15476286.2025.2498203","DOIUrl":"https://doi.org/10.1080/15476286.2025.2498203","url":null,"abstract":"<p><p>Dysregulated translation is a hallmark of cancer, and recent genome-wide studies in tumour cells have uncovered widespread translation of non-canonical reading frames that often initiate at non-AUG codons. If an upstream non-canonical start site is located within a frame with an annotated coding sequence (CDS), such translation events can lead to the production of proteoforms with altered N-termini (PANTs). Certain examples of PANTs from oncogenes (e.g. c-MYC) and tumour suppressors (e.g. PTEN) have been previously linked to cancer. We have performed a systematic computational analysis on recently identified non-AUG initiation-derived N-terminal extensions of cancer-associated proteins, and we discuss how these extended proteoforms may acquire new oncogenic properties. We identified a loss of stability for the N-terminally extended proteoforms of oncogenes TCF-4 and SOX2. Furthermore, we discovered likely functional short linear motifs within the N-terminal extensions of oncogenes and tumour suppressors (SOX2, SUFU, SFPQ, TOP1 and SPEN/SHARP) that could provide an explanation for previously described functionalities or interactions of the proteins. In all, we identify novel cases where PANTs likely show different localization, functions, partner binding or turnover rates compared to the annotated proteoforms. Therefore, we propose that alterations in the stringency of translation initiation, often seen under conditions of cellular stress, may result in reprogramming of translation to generate novel PANTs that influence cancer progression.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-18"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alongshan virus: An emerging arboviral challenge in regional health security.","authors":"Meixi Ren, Zheng Pang, Yingxin Tu, Anan Wang, Tao Xu, Xiaoli Yu, Guoyu Niu","doi":"10.1080/21505594.2025.2492360","DOIUrl":"https://doi.org/10.1080/21505594.2025.2492360","url":null,"abstract":"<p><p>The Alongshan virus (ALSV), classified within the Flaviviridae family and belonging to the Jingmenvirus group, is a segmented RNA virus that was first identified in China in 2017. Since then, it has been reported in several Eurasian countries. Although no confirmed fatal cases have been documented, the potential public health risks associated with ALSV are significant and warrant serious attention. The emergence of ALSV has not only broadened the array of tick-borne diseases but has also enriched the research landscape surrounding segmented flaviviruses. Despite these advancements, our understanding of ALSV is still nascent, and its complex infection pathways remain largely unexplored. This review seeks to offer an in-depth examination of ALSV, addressing its biological properties, molecular features, epidemiological data, clinical presentations, and diagnostic methodologies. Our objective is to promote progress in the formulation of preventive, diagnostic, and therapeutic measures for this emerging segmented flavivirus.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2492360"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-02-20DOI: 10.1080/15592294.2025.2466382
Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack
{"title":"Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes.","authors":"Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack","doi":"10.1080/15592294.2025.2466382","DOIUrl":"10.1080/15592294.2025.2466382","url":null,"abstract":"<p><p>Lung carcinogenesis is causally linked to cigarette smoking, in part by epigenetic changes. We tested whether accumulated epigenetic change in smokers is apparent in bronchial basal cells as cells of origin of squamous cell carcinoma. Using an EM-seq platform covering 53.8 million CpGs (96% of the entire genome) at an average of 7.5 sequencing reads per CpG site at a single base resolution, we evaluated cytology-normal basal cells bronchoscopically brushed from the in situ tobacco smoke-exposed 'bronchial epithelial field' and isolated by short-term primary culture from 54 human subjects. We found that mean methylation was globally lower in ever (former and current) smokers versus never smokers (<i>p</i> = 0.0013) across promoters, CpG shores, exons, introns, 3'-UTRs, and intergenic regions, but not in CpG islands. Among 6mers with dinucleotides flanking CpG, those containing CGCG showed no effect from smoking, while those flanked with TT and AA displayed the strongest effects. At the gene level, smoking-related differences in methylation level were observed in <i>CDKL1, ARTN</i>, <i>EDC3</i>, <i>CYP1B1</i>, <i>FAM131A</i>, and <i>MAGI2</i>. Among candidate cancer genes, smoking reduced the methylation level in <i>KRAS</i>, <i>ROS1</i>, <i>CDKN1A</i>, <i>CHRNB4</i>, and <i>CADM1</i>. We conclude that smoking reduces long-term epigenome-wide methylation in bronchial stem cells, is impacted by the flanking sequence, and persists indefinitely beyond smoking cessation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2466382"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Porcine cGAS-STING signalling induced apoptosis negatively regulates STING downstream IFN response and autophagy via different mechanisms.","authors":"Nengwen Xia, Anjing Liu, Hongjian Han, Sen Jiang, Qi Cao, Jia Luo, Jiajia Zhang, Weilin Hao, Ziyan Sun, Nanhua Chen, Huiling Zhang, Wanglong Zheng, Jianzhong Zhu","doi":"10.1080/21505594.2025.2496436","DOIUrl":"https://doi.org/10.1080/21505594.2025.2496436","url":null,"abstract":"<p><p>The innate immune cGAS-STING signalling pathway recognizes double-stranded DNA and induces the interferon (IFN) response, autophagy and apoptosis, exerting a broad antiviral effect. However, the mechanisms and interrelationship between STING induced downstream IFN, autophagy, and apoptosis in livestock have not been fully elucidated. Our previous study defined porcine STING (pSTING) induced IFN, autophagy and apoptosis, and showed that IFN does not affect autophagy and apoptosis, whereas autophagy inhibits both IFN and apoptosis, likely by promoting pSTING degradation. In this study, we further explored the underlying mechanism of pSTING induced apoptosis and the regulation of IFN and autophagy by apoptosis. First, pSTING induces endoplasmic reticulum (ER) stress and mitochondrial damage to activate caspases 9, 3, and 7, which drive intrinsic apoptosis. Second, pSTING triggered apoptosis inhibits the IFN response by activating caspase 7, which cleaves pIRF3 at the species specific D197/D198 site. Third, pSTING activated apoptotic caspases 9, 3, and 7 reduce the expression of ATG proteins, and cleave the ATG5-ATG12L1 complex, effectively inhibiting autophagy. Fourth, knockout of pSTING activated apoptosis heightens the IFN response and autophagy, while suppressing the replication of Herpes Simplex Virus type 1 (HSV-1), Vesicular Stomatitis Virus (VSV) and Pseudorabies Virus (PRV). This study sheds light on the molecular mechanisms of innate immunity in pigs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2496436"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}