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Results for “host gene expression”

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PubMed1977

Development of Escherichia coli virus T1: repression of host gene expression.

Host protein synthesis, measured either as amino acid incorporation into proteins or as enzyme synthesis, is inhibited rapidly after infection Escherichia coli with T1. Analysis of this inhibition, using a technique which distinguishes between translation and transcription, revealed that translation of host mRNA is specifically blocked. Comparison of the time course of T1-induced host repression with inhibition by the drugs rifampicin, nitrofurantoin and chloramphenicol showed that T1 affects the initiation step of host translation. Intact membranes are apparently essential for host repression, suggesting a membrane-mediated process. Concomitant viral protein synthesis is not required. The membrane-altering principle is a constituent of the viral particle.

Bacterial Proteins↗

PubMed2026

Multi-level aggregation analysis of microbiome composition and host gene expression reveals associations with systemic and local immunity.

The human gut microbiome plays a critical role in immune regulation, yet the molecular links between microbiome composition and host gene expression remain incompletely understood. We analyzed associations between host gene expression and microbiome composition in a cohort of 315 healthy individuals, integrating microarray-based gene expression data from three intestinal sites (ileum, transverse colon, and rectum) and six immune cell types with microbiome sequencing data. Using a hierarchical feature aggregation strategy combining principal component analysis, clustering, and covariate correction, we discovered significant associations primarily related to immunity. While microbial profiles were similar across the three intestinal sites, the transverse colon yielded the most "microbiome-host gene expression" associations. Among the immune cell types, CD8+ cells showed the highest number of associations. The first principal component of microbiome composition, reflecting a gradient from commensals (e.g., Ruminococcaceae and Christensenellaceae) to proinflammatory taxa ([Ruminococcus] gnavus and Lachnoclostridium), correlated with the expression of TNF-α-linked genes (HMOX1, CPI17, HSD3B2, and SLC5A1). Among individual genera, Catenibacterium abundance was associated with gene expression in both intestinal and immune cells, including negative associations with MRPS21 (related to mitochondrial function) in the transverse colon and with CD8+ gene programs related to T cell differentiation. These findings align with emerging evidence implicating mitochondrial dysfunction in intestinal inflammation. Our results identify multi-level associations between the gut microbiome and host gene expression, suggesting potential mechanisms by which microbiota shape local and systemic immunity and vice versa. The implicated genes and taxa represent candidates for experimental validation to improve understanding of host-microbiome homeostasis and its disruption in disease.IMPORTANCEThe gut microbiome and immune system are engaged in a complex interplay throughout human life. While most associative studies focus on case-control comparisons-typically examining patients with conditions such as inflammatory bowel disease or metabolic diseases-less is known about the molecular links between the microbiome and immune system in healthy individuals. In this study of a large cohort of healthy individuals, we addressed this gap by applying multiscale modeling to tackle the high dimensionality of host-microbiome data. We identified multi-level associations between microbiome composition and host gene expression in both intestinal tissues and immune cells. These findings offer a valuable reference for understanding baseline host-microbiome communication and highlight molecular candidates-such as TNF-α-related genes and mitochondrial pathways-for future experimental validation.

Humans↗

PubMed2026

Blood-derived gene expression profiles associated with dietary microalgae oil intake and methane emission variation in lambs.

BACKGROUND: Minimising methane (CH4) emissions from livestock production is a global priority, and feed modifications, such as supplementing diets with microalgae, have previously been shown to help reducing enteric CH4 production. This study explored blood-derived host gene expression profiles from twenty lambs supplemented with increasing levels of microalgae oil to investigate their transcriptional responses associated with varying microalgae oil levels while also exploring the host systemic responses towards varied CH4 productions. RESULTS: Findings revealed no significant changes in CH4 production with increasing levels of microalgae oil intake through phenotypic analysis (P = 0.18). However inter-individual variations in CH4 production ranged from 27.02 to 47.86 g/day throughout the study period. Blood RNA-Sequencing identified 64 significant genes including DHCR7, DHCR24, HMGCS1, INSIG1, LSS, MSMO1, and SQLE, which were involved in lipid metabolism, and steroid biosynthesis that became enriched alongside increasing microalgae oil intake levels thereby contributing to a positive impact on lambs' metabolic functions. Additionally, seven significant blood-expressed host genes (NME4, MARCHF3, PLXNB3, LOC132657460, LOC121819234, LOC105603087, LOC101116551) functionally enriched in nucleotide metabolic pathways and immune responses were identified to have significant positive associations with increasing CH4 production. Importantly, this study found no overlap between genes associated with microalgae oil intake and those linked to CH4 emissions. CONCLUSIONS: Findings suggest that microalgae oil intake and inter-individual variations in CH₄ production are associated with distinct blood-derived transcriptional responses. Although such signals should be interpreted as proxies for systemic host responses rather than direct measures of rumen-specific processes, these results emphasise the importance of considering host-associated molecular variations alongside dietary CH₄-mitigation strategies.

Animals↗

PubMed1977

Development of E.coli virus T1: the pattern of gene expression.

T1 infected bacteria exhibit a distinct pattern of gene expression. The control of this expression is accessible to biochemical analysis. T1 induces the synthesis of 31 proteins in E. coli. The virion contains 15 proteins. By means of T1 amber mutants, 10 gene products have been assigned to specific T1 genes. Three classes of T1 proteins are defined by the kinetics of their syntheses: early, early-late and late proteins. The regulation of protein synthesis involes at least three mechanisms: for cessation of host gene expression, for discontinuation of the early class during the late phase and for induction of the late T1 proteins. The positive control of late gene expression is not coupled to replication. The host RNA-polymerase transcribes the viral genome throughout the infectious cycle. No virus coded RNA-polymerase is induced.

Bacterial Proteins↗

PubMed2025

Symbionts with eroded genomes adjust gene expression according to host life-stage and environment.

Symbiotic bacteria in long-term host associations frequently undergo extreme genome reduction. While they retain genes beneficial to the host, their repertoire of transcription factors is severely reduced. Here, we assessed whether genome-eroded symbionts can still regulate gene expression by characterizing the transcriptional responses of obligate symbionts in reed beetles to different temperatures and host life stages. These symbionts feature a small genome (~0.5 Mb), encoding for 9-10 essential amino acid biosynthesis pathways, 0-2 pectinases, and 4-5 transcription factors. We found that the symbionts respond to winter conditions by upregulating a heat-shock sigma factor and downregulating translation machinery. Across life stages, symbionts adjusted gene expression to meet the hosts' nutritional demands, upregulating amino acid biosynthesis in larvae, while expression and activity of host and symbiont enzymes involved in plant cell wall breakdown increased in the folivorous adults. In addition, the regulation of symbiont cell morphology genes corresponded to cell shape differences across life stages. Thus, reed beetle symbionts may use their few transcription factors to respond to the host's environment, highlighting the regulatory potential of long-term coevolved symbionts despite severely reduced genomes.

Symbiosis↗

PubMed2026

Trimethylamine-producing microbe Bacillus megaterium KCTC 3007 promotes antitumor immunity in endometrial cancer via type I interferon response pathways.

BACKGROUND: Endometrial cancer (ECa) is one of the most common gynecologic malignancies, with limited therapeutic responses in metastatic or recurrent cases. The bacterial microbiota has emerged as a key modulator of carcinogenesis and antitumor immunity. However, the role of endometrial microbiota in ECa pathogenesis and prognosis remains poorly understood. METHODS: We performed comprehensive multi-omics analysis integrating metatranscriptomics, transcriptomics, and targeted metabolomics from 60 ECa and 18 benign patients. RNA sequencing enabled simultaneous profiling of active tissue-resident microbiota and host gene expression. Serum metabolomics was conducted on all patients. Identified microbial-metabolite associations were validated through in vitro co-culture experiments using peripheral blood mononuclear cells (PBMCs), cancer cell lines, RNA sequencing, and live cell imaging. RESULTS: ECa patients exhibited significantly altered microbial diversity and composition compared to benign controls. Through integrated multi-omics analysis, we identified Bacillus megaterium (BM) KCTC 3007 as a beneficial microbe associated with prolonged recurrence-free survival. In an exploratory analysis of ECa subtypes, Cupriavidus taiwanensis and Marinomonas primoryensis showed potential links to poor prognosis, although these observations warrant caution due to the limited size of certain subgroups. Tissue BM abundance positively correlated with serum trimethylamine N-oxide (TMAO) levels, particularly in postmenopausal women. In vitro experiments demonstrated that BM KCTC 3007 enhanced antitumor immunity by promoting interleukin and type I interferon expression, expanding CD8 + T cell populations, and increasing immune cell-tumor cell interactions. RNA sequencing revealed activation of interferon alpha response and immune cell proliferation pathways, with IFNAR1 identified as a key upstream regulator. TMAO treatment recapitulated these immune-activating effects, enhancing CD8 + T cell responses and preferentially inducing pyroptotic cancer cell death. CONCLUSIONS: We provide the first evidence that tissue-resident BM KCTC 3007 promotes antitumor immunity in ECa through TMAO production and subsequent type I interferon-mediated immune activation. This integrated multi-omics approach establishes a complete microbe-metabolite-host mechanistic pathway and highlights the therapeutic potential of TMAO-producing probiotic strains for ECa treatment. Video Abstract.

Female↗

PubMed2026

Sea urchin co-culture boosts abalone growth by reducing environmental stress and remodeling gut microbiota.

Biofouling and microenvironmental deterioration are major bottlenecks restricting the intensive aquaculture of Pacific abalone (Haliotis discus hannai). While co-culturing offers an eco-friendly mitigation strategy, the underlying mechanisms promoting abalone growth remain poorly understood. This study evaluated the growth performance of H. d. hannai co-cultured with varying densities of the sea urchin (Strongylocentrotus intermedius). By employing transcriptome and 16S rRNA sequencing of the abalone gut, we investigated the synergistic responses of host gene expression and gut microbiota. Compared with the monoculture group, the co-culture groups showed significantly less biofouling and greater growth of abalone, with the co-culture (n = 15) exhibiting the best outcomes. Transcriptomic analysis revealed 1444, 760, and 508 DEGs in G5, G10, and G15, respectively, compared with G0. These DEGs were significantly enriched in metabolic pathways, including glycolysis and sterol metabolism, indicating a shift in intestinal energy metabolism from stress defense toward growth under co-culture conditions. Gut microbiota profiling identified Proteobacteria and Firmicutes as the dominant phyla, with specific functional taxa (e.g., Psychrilyobacter and Akkermansia) enriched in a density-dependent manner. Furthermore, correlation analysis demonstrated that growth traits positively correlated with growth-promoting taxa (e.g., the unclassified AB1 lineage), but negatively correlated with potentially opportunistic taxa (e.g., Tabrizicola). These findings provide insights into a potential synergistic mechanism of "environmental stress alleviation-metabolic reprogramming-microecological remodeling" driving abalone growth, providing a theoretical foundation for optimizing co-culture systems and developing growth-associated biomarkers.

Animals↗

PubMed2026

Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection.

Amino acid levels fluctuate across diverse pathological conditions. Whether such amino acid modulations directly shape pathophysiology by regulating host gene expression remains unknown. We found that extracellular arginine restriction, observed in cancer and infection, represses specific arginine tRNAs-directly suppressing translation of major histocompatibility complex I (MHC class I) and antigen presentation. Arginine regulation of MHC class I was codon-usage dependent, as synonymous codon mutations prevented MHC class I modulation. Dietary arginine restriction impaired anti-viral immunity against influenza and SARS-CoV-2 and increased colon tumorigenesis. Conversely, increasing arginine availability via dietary supplementation or myeloid-specific arginase 1 deletion enhanced MHC class I protein levels, suppressed colon tumorigenesis, and improved viral infection outcomes. These disease-modulating effects were abolished in β2-microglobulin (B2m)-deficient mice. Thus, dietary modulation of a single amino acid critically influences codon-biased translation and MHC class I-mediated immunity to respiratory viral infections and cancer, revealing an unexpected mechanism and disease hazard for arginine deficiency and highlighting potential for amino acid-based translation modulation therapy.

Animals↗

PubMed2026

In vivo porcine multi-omics integration identifies microbiome-driven histamine elevation and lasting gut perturbations following Ascaris suum infection and fenbendazole treatment.

Ascaris roundworms impair human and swine health. While treatments using anthelmintic drugs are generally effective in eliminating worms, their effects on the gut microenvironment remain poorly understood. Here we applied integrated multi-omics to characterize infection- and treatment-associated alterations in the pig-Ascaris system. In vitro anaerobic cultures were conducted as supportive validation of selected observations. Ascaris suum infection altered microbial composition and dysregulated 182 serum and fecal metabolites, including histamine and p-cresol sulfate. Compared with time-matched uninfected controls, infected pigs treated with fenbendazole showed marked differences in gut microbial composition 13 days after confirmed worm clearance. Eleven microbial pathways were enriched in successfully treated pigs, including peptidoglycan biosynthesis and histidine metabolism, indicating that infection-associated alterations may persist after treatment. In vitro co-exposure of Lactobacillus reuteri to fenbendazole and A. suum proteins increased histamine production by approximately 79% at 48 h (p < 0.05), serving as supportive evidence of a microbiome contribution. Collectively, our in vivo findings support that host-microbiota-parasite interactions are multifaceted. Microbiota-derived metabolites were associated with regulation of host gene expression, such as TFF2 and IL8. Microbiota plasticity allows the exploitation of the niche differentiated upon infection, resulting in the proliferation of certain Lactobacillus strains in treated animals. Nevertheless, interpretations of treatment effects are made cautiously given the absence of an uninfected drug-only group and the cross-sectional design. Understanding these complex interactions will be important for the design of next-generation functional anthelmintics.

Animals↗

PubMed2026

Friends or foes: Unraveling the tsetse fly-Spiroplasma symbiosis.

Tsetse flies (Glossina spp.) transmit African trypanosomes, the causative agents of human African and African animal trypanosomiases (HAT and AAT, respectively). These neglected tropical diseases impose significant public health and economic burdens across sub-Saharan Africa. Trypanosome transmission by tsetse flies is influenced by multiple factors, including host genetic background, ecological factors, and interactions with heritable microbial endosymbionts. Spiroplasma glossinidia has recently emerged as an important modulator of tsetse reproductive fitness and vector competence, making it a potential target for symbiont-based vector control strategies. In this review, we summarize the current knowledge of the tsetse-Spiroplasma symbiosis. We detail Spiroplasma's spatial and temporal infection dynamics in laboratory-reared and natural populations. Additionally, we highlight key aspects of the bacterium's genomics, phylogenetics, and physiological interactions with its tsetse host, including influences on host gene expression reproductive physiology, and vector competence. Finally, we discuss how the tsetse-Spiroplasma symbiosis could be harnessed to develop innovative, biological-based vector control and trypanosome transmission-blocking strategies, and we identify critical gaps that must be addressed to translate these findings into effective disease control interventions.

Animals↗

PubMed1979

Polyoma virus and cyclic AMP-mediated control of dihydrofolate reductase mRNA abundance in methotrexate-resistant mouse fibroblasts.

As a model cell culture system for studying polyoma-mediated control of host gene expression, we isolated methotrexate-resistant 3T6 cells in which one of the virus-induced enzymes, dihydrofolate reductase, is a major cellular protein. In highly methotrexate-resistant cell lines dihydrofolate reductase synthesis accounts for over 10% that of soluble portein, corresponding to an increase of approximately 100-fold over the level in parental cells. This increase in dihydrofolate reductase synthesis is due to a corresponding increase in the abundance of dihydrofolate reductase mRNA and gene sequences. We have used these cells to show that infection with polyoma virus results in a 4- to 5-fold increase in the relative rate of dihydrofolate reductase synthesis and a corresponding increase in dihydrofolate reductase mRNA abundance. The increase in dihydrofolate reductase synthesis begins 15 to 20 h after infection and continues to increase until cell lysis. These observations represent the first direct evidence that viral infection of eukaryotic cells results in the increased synthesis of a specific cellular enzyme and an increase in the abundance of a specific cellular mRNA. In order to gain additional insight into the control of dihydrofolate reductase synthesis we examined other parameters affecting dihydrofolate reductase synthesis. We found that the addition of fresh serum to stationary phase cells results in a 2-fold stimulation of dihydrofolate reductase synthesis, beginning 10 to 12 h after serum addition. Serum stimulation of dihydrofolate reductase synthesis is completely inhibited by the presence of dibutyryl cyclic AMP as well as by theophylline or prostaglandin E1, compounds which cause an increase in intracellular cyclic AMP levels. In fact, the presence of dibutyryl cyclic AMP and theophylline results in a 2- to 3-fold decrease in the rate of dihydrofolate reductase synthesis and the abundance of dihydrofolate reductase mRNA. However, in contrast to the effect on serum stimulation, dibutyryl cyclic AMP and theophylline do not inhibit polyoma virus induction of dihydrofolate reductase synthesis or dihydrofolate reductase mRNA levels. These observations suggest that dihydrofolate reductase gene expression is controlled by at least two regulatory pathways: one involving serum that is blocked by high levels of cyclic AMP and another involving polyoma induction that is not inhibited by cyclic AMP.

Bucladesine↗

PubMed1978

Exclusion of bacteriophage T1 by bacteriophage lambda. I. Early exclusion requires lambda N gene product and host factors involved in N gene expression.

Two modes of exclusion of T1 by lambda are distinguished. "Early" exclusion depends on gene N, but not on gene Q. It is at least partially ineffective against T1am23. "Late" exclusion depends on gene Q and effects T1am23 as well as T1+. Early exclusion is a direct effect of N gene product, rather than N gene being required for the expression of some other lambda gene. Three host mutations, groN, nusA, and nusB, known to interfere with lambda replication by affecting N gene expression, also interfere with the ability of lambda to exclude T1.

Coliphages↗

PubMed2025

Dual RNA isolation from blood: an optimized protocol for host and bacterial RNA purification for dual RNA-sequencing analysis in whole blood sepsis samples.

Dual RNA-sequencing (dual RNA-seq) holds significant promise for deciphering bacterial virulence mechanisms during systemic infections. However, its application in sepsis research is hindered by technical challenges, including a low bacterial burden in blood and limited sample volumes and RNA yield from vulnerable populations, such as neonates. We developed an optimized protocol [dual RNA isolation from blood (DRIB)] for simultaneous stabilization, isolation and purification of high-quality host leukocyte and bacterial RNA from low-volume whole blood samples (0.5 ml). This protocol is compatible with clinical sample collection workflows and high-throughput RNA sequencing. The feasibility of DRIB for dual RNA-seq was validated using a pilot cohort of clinical adult sepsis samples, enabling the investigation of host-bacterial gene expression during sepsis. The DRIB protocol yielded 2.10-6.91 µg of total RNA per clinical sample in our pilot cohort. Dual-species ribosomal RNA (rRNA) depletion and RNA-seq generated 16.6-24.8 million filtered reads per sample, with 63±7% of reads uniquely mapped to host or bacterial sequences. Host genes accounted for 51-68% (8.4-10.9 million) reads, while 0.5-6.7% (79,496-789,808 reads) mapped to bacterial genomes. Bioinformatic analysis revealed that both shared and individual transcriptional patterns were identified in host and bacterial responses, including pathways related to immune metabolism and metal-ion binding. Our optimized DRIB protocol and RNA-seq pipeline effectively captured both host and bacterial RNA transcription in clinical sepsis samples. Expanding this approach to larger cohorts and varying disease timepoints will provide crucial new insights into host-bacterial gene co-expression dynamics in sepsis progression and outcomes.

Humans↗

PubMed2025

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 recruits the host protein CTCF to viral episomes to control the differentiation-dependent viral transcriptional programme. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18 may also manipulate CTCF to contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression.

Humans↗

PubMed2026

Host-aware Identification of Intrinsic Gene Expression Biopart Parameters using Combinatorial Libraries.

Model-based design in synthetic biology is limited because bioparts are typically characterised by relative metrics that vary across genetic and physiological contexts. To address this, we introduce a host-aware framework for quantitatively characterising bioparts in combinatorial libraries of plasmid-based constitutive expression constructs. The approach integrates a digital twin of Escherichia coli, conditioned on measured growth rate, with model-in-the-loop parameter identification to separate biopart-associated properties from host-dependent effects. Using structured combinatorial libraries, we identify mechanistically interpretable, transferable parameters for plasmid origins, promoters and ribosome binding sites. In particular, we define an intrinsic translation initiation capacity that captures the dominant RBS-associated contribution to translation while context-dependent expression emerges from host physiology and local sequence context. The resulting parameterisation accurately predicts protein synthesis across physiological conditions, supports incremental library expansion, and reveals localised failures of modularity, providing a scalable foundation for predictive host-aware design in synthetic biology.

Escherichia coli↗

PubMed2026

Dual-transcriptomic analysis of human nasal transcriptome and microbiome reveals host-bacteria associations in symptomatic respiratory infection.

BACKGROUND: The human nasopharynx is colonized by a diverse community of commensal microbiota linked to many respiratory diseases, yet their associations with the host remain unclear. RESULTS: In this study, we introduced a dual-transcriptomics analysis strategy, which can characterize the host transcriptome and microbiome from nasal samples simultaneously. We applied this workflow to a local SARS-CoV-2 cohort with 76 asymptomatic infected patients, among whom 52 (68.42%) developed symptomatic infection during a 1-week follow-up period. Nasal swabs were collected from all 76 patients at enrollment and from 73 patients at one-week later follow-up. We detected a median of 8.94% reads that did not map to the human genome across all 149 samples, among which around half (median 49.68%) were successfully mapped to microbiome genome. Meta-transcriptomic analysis detected significantly higher SARS-related coronavirus loads in samples from the symptomatic group at enrollment (P = 0.004), and both groups showed decreased loads one week later (symptomatic, P = 0.001; asymptomatic, P = 0.035). Compared with benchmarking 16 S rRNA sequencing on 53 samples, our computational strategy showed high correlation of relative abundance in all top 20 genera (median Rho = 0.90, Pmax < 0.001). A total of 670 bacteria species were identified to show a relative abundance ≥ 0.01% in at least 10% samples. Differential abundance analysis identified 76 species (DASs) from six phyla with significantly decreased abundance in samples from the symptomatic group (log2(fold change or FC) < -1 and adjusted P < 0.05) compared to the asymptomatic group at enrollment. Integrating these symptom-associated DASs with host's gene expression using an expression quantitative trait bacteria (eQTB) model, we found 45 symptom-associated DASs identified at enrollment were significantly associated with one to 14 genes (adjusted P < 0.05). GSEA showed a series of symptom-associated DASs were significantly correlated with pathways related to olfactory function, keratinocyte differentiation, and DNA methylation. CONCLUSIONS: In summary, our dual-transcriptomic analysis strategy effectively characterized host-microbiome associations, offering insights into microbial contributions to respiratory diseases.

Humans↗

PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗

PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60 days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗