Biochemistry and Biophysics Reports最新文献

{"title":"Distinct hyaluronan content and hierarchical organization of collagen-elastic fiber assemblies in subcutaneous fascia","authors":"Natsuki Maeda ,&nbsp;Kenshi Togashi ,&nbsp;Yongchol Shin ,&nbsp;Yasutada Imamura","doi":"10.1016/j.bbrep.2026.102536","DOIUrl":"10.1016/j.bbrep.2026.102536","url":null,"abstract":"<div><div>Previous studies have demonstrated that the subcutaneous fascia is a continuous connective tissue layer consisting of morphologically distinct “loose regions” and “dense regions”. However, the molecular basis of this regional heterogeneity remains unclear. This study aimed to analyze the biochemical and compositional differences between these two regions to elucidate the factors responsible for their functional and structural distinctions. Loose and dense fascia were isolated from chicken subcutaneous fascia and subjected to collagen composition analysis using SDS-PAGE, hyaluronan (HA) quantification, and fluorescence and electron microscopy combined with various biochemical treatments.</div><div>The results showed no significant differences in the composition ratios of major fibrillar collagens (types I, III, and V) or in total collagen content per dry weight between the two regions. In contrast, significant differences were found in non-collagenous matrix components; specifically, loose fascia contained approximately twice as much HA as dense fascia (loose: 0.31%, dense: 0.15%). Collagen hybridizing peptide (CHP) staining, which detects denatured/disrupted collagen chains, showed strong signals at the bundle boundaries in dense fascia, suggesting region-specific differences in supramolecular organization and locally increased collagen triple-helix dynamics/instability at bundle peripheries. In addition, elastase treatment led to loosening/disruption of collagen bundles, an observation consistent with a contribution of elastic-fiber components to maintaining higher-order bundle integrity, although enzyme purity and secondary mechanical effects cannot be fully excluded.</div><div>These results suggest that the regional mechanical behaviors are not fully explained by differences in major collagen composition and are more strongly associated with differences in hyaluronan abundance and supramolecular organization. These findings provide a molecular and ultrastructural basis that may underlie the distinct mechanical behaviors previously reported for loose and dense regions of the subcutaneous fascia.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102536"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID","authors":"Vjera Ramer ,&nbsp;Gert A. van Montfrans","doi":"10.1016/j.bbrep.2026.102518","DOIUrl":"10.1016/j.bbrep.2026.102518","url":null,"abstract":"<div><div>An explanation for long COVID (LC) and its many symptoms remains elusive, and no unifying upstream mediator of its pathophysiology has yet been identified. Viral infections, including COVID-19, upregulate Prostaglandin E2 (PGE2), - the principal lipid mediator of inflammation. PGE2 has broad paracrine effects, including modulation of autoantibodies, nervous systems, blood pressure, glucose levels, and apoptosis. Upregulated, PGE2 may drive multiple pathological processes through its four receptors: EP1-EP4. Through EP3, PGE2 stimulates characteristic viral sickness symptoms. Both severe and mild disease may precede LC, possibly reflecting either excessive or insufficient EP3 activity, which we term “EP3 up” and “EP3 down”, respectively. In individuals with “EP3 up” or “EP3 down” states, elevated PGE2 levels may disrupt homeostasis. Diverse physical and mental stressors upregulate PGE2. Data suggest that multiple hormones and agents stimulate PGE2 production, while PGE2 reportedly antagonizes these agents, possibly functioning as a homeostatic limiter. Sufficiently elevated PGE2, “PGE2 dominance”, may interfere with their activity through inhibiting their release, overlapping subcellular signaling pathways or by stimulating phosphorylation and autoantibodies. Homeostatic elevations of PGE2-stimulating hormones, together with other PGE2-raising factors, may promote resistance to these hormones, resulting in persistent PGE2 upregulation. Literature suggests that PGE2 overactivity, mediated by imbalanced EP receptor signaling, aligns with the diverse symptomatology of LC. Based on our literature analysis, we propose that persistent upregulation of PGE2 plays a pivotal role in the development of LC. Consequently, validation of elements of this framework may help guide exploration of therapeutic strategies targeting PGE2 pathways or EP receptor regulation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102518"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin alleviates CCl4-induced liver fibrosis via regulating gut microbiota and the AGE-RAGE/PI3K/Akt signaling axis","authors":"Yi Tang ,&nbsp;Yu-Han Jiang ,&nbsp;Chen-Yang Wu ,&nbsp;Guo-Tai Wang ,&nbsp;Meng-Lan Li","doi":"10.1016/j.bbrep.2026.102540","DOIUrl":"10.1016/j.bbrep.2026.102540","url":null,"abstract":"<div><div>The absence of clinically effective anti-fibrotic agents for chronic liver disease represents a critical therapeutic gap. Although the flavonoid quercetin exhibits potent experimental anti-fibrotic activity, its full integrative mechanisms—particularly those involving gut-liver axis crosstalk and specific signaling pathways—remain incompletely elucidated. To address this, we employed an integrated methodological approach encompassing network pharmacology, molecular docking, a CCl₄-induced murine model of liver fibrosis, 16S rRNA sequencing, and molecular validation to delineate quercetin's anti-fibrotic actions. Network analysis identified tumor necrosis factor (TNF), protein kinase B (Akt1), interleukin-6 (IL-6), and the AGE-RAGE/PI3K/Akt signaling axis as core targets and pathways, findings further corroborated by strong molecular binding affinities. In vivo, quercetin administration reversed CCl₄-induced body weight loss, ameliorated hepatic injury, reduced fibrogenesis markers, and attenuated pathological collagen deposition. Critically, quercetin restructured gut microbiota composition, enhancing α-diversity indices and favorably modulating the Bacteroidetes and Firmicutes ratio. Western blot analysis revealed quercetin's anti-fibrotic mechanism involves a dual inhibitory effect: primarily downregulating hepatic RAGE expression and concurrently suppressing PI3K-Akt pathway phosphorylation. These findings establish that quercetin ameliorates liver fibrosis through synergistic gut microbiota reprogramming and targeted disruption of the pathogenic AGE-RAGE/PI3K/Akt signaling axis, providing a mechanistic foundation for therapeutic development.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102540"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated biophysical fragment screening approach identifies novel binders of the CD28 immune receptor","authors":"Laura Calvo-Barreiro,&nbsp;Hossam Nada,&nbsp;Moustafa T. Gabr","doi":"10.1016/j.bbrep.2026.102542","DOIUrl":"10.1016/j.bbrep.2026.102542","url":null,"abstract":"<div><div>CD28 is an essential costimulatory receptor required for full T cell activation and its dysregulation contributes to multiple immune-mediated pathologies. Despite its central immunological role, CD28 remains largely unexplored as a target for small-molecule modulation, primarily due to the shallow and large interface of its ligand-binding site. Here, we applied a fragment-based high-throughput screening (HTS) strategy to identify low molecular weight chemotypes capable of engaging with human CD28. A 3200-member library composed of structurally diverse fragments, enriched for scaffolds designed to target protein-protein interaction (PPI) interfaces, was screened in single-dose format using temperature-related intensity change (TRIC) technology, yielding 36 primary hits (1.13% hit rate). Follow-up surface plasmon resonance (SPR) validation confirmed two fragments as direct CD28 binders. Molecular docking analysis revealed a plausible binding orientation for PPIF3 within the CD28 extracellular domain, suggesting potential interaction hotspots that may be exploited during future optimization. Together, these findings provide the first demonstration that fragment-based screening can successfully identify chemotypes capable of engaging with the CD28 PPI interface. This work establishes a scalable, biophysics-driven workflow for CD28 ligand discovery and lays the foundation for subsequent hit-to-lead development of small molecule CD28 modulators.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102542"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation genetic testing for polygenic diseases: A novel paradigm in embryo selection","authors":"Tianrui Jing ,&nbsp;Yanzhi Du","doi":"10.1016/j.bbrep.2026.102532","DOIUrl":"10.1016/j.bbrep.2026.102532","url":null,"abstract":"<div><div>Polygenic diseases are caused by a number of independently acting or interacting polymorphic genomic variants in conjunction with environmental factors, and show an increasing global prevalence, posing a significant threat to individual and public health. Given the limited curative prospects for polygenic diseases owing to their complex etiology, preventive strategies have gained paramount importance. Preimplantation genetic testing for polygenic disorders (PGT-P) is an advanced in vitro fertilization technique that screens embryos for genetic susceptibility to polygenic diseases, aiming to reduce the risk of offspring developing conditions such as diabetes, schizophrenia, polycystic ovary syndrome, and certain cancers. This technology calculates polygenic disease risks across sibling embryos relying on the use of a polygenic risk score (PRS) that counts the effects of risk alleles derived from genome-wide association studies. Using PGT-P, each embryo's PRS is computed for any disease or trait of interest, and the euploid embryo with the lowest PRS is prioritized for implantation. As a result, PGT-P may decrease the disease risk for future offspring and provide a novel strategy for embryo ranking, selection, or even discarding. In this review, we systematically summarize the current knowledge regarding PGT-P, detailing its workflow, potential benefits, predictive power, expected risk reduction and significant limitations. We further evaluate its utility and practical implementation in clinical practice and outline critical directions for future research.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102532"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular identification and phylogenetic analysis of marmots in the Xinjiang's Altai Mountains, a newly discovered plague focus of China","authors":"Qiguo Wang ,&nbsp;Mailihaba Baikeli ,&nbsp;Yongjun Luo ,&nbsp;Xijiang Wang ,&nbsp;Yi Zhang ,&nbsp;Jun Zhao ,&nbsp;Remila Tuerhong ,&nbsp;Maidina Xiaokaiti ,&nbsp;Azhati Rehemu ,&nbsp;Xinhui Wang ,&nbsp;Wenting Mou","doi":"10.1016/j.bbrep.2026.102539","DOIUrl":"10.1016/j.bbrep.2026.102539","url":null,"abstract":"<div><div>The Altai Mountains in Xinjiang have been recognized as a new plague focus in China since 2023. Although previous morphological studies suggested that marmots in this region belong to <em>Marmota baibacina</em>, this classification remained unconfirmed at the molecular level. In this study, 37 marmot samples were collected: including 10 <em>M. baibacina</em> from the northern Tianshan Mountains, 9 <em>M. baibacina</em> from the southern Tianshan Mountains, and 18 unverified individuals from the Altai Mountains. The <em>COI</em>, <em>Cytb</em>, and <em>D-loop</em> gene fragments were sequenced and subjected to phylogenetic analysis. Homology comparisons revealed greater than 95% sequence identity across all samples, with all matches corresponding to marmot populations. Genetic distances between groups (1%–7%) exceeded those within groups (0%–2%). <em>F</em>_<em>st</em> values among populations ranged from 0.55780 to 0.98449, indicating significant differentiation, particularly between the southern Tianshan population and the other two groups. In contrast, genetic divergence between the Altai and northern Tianshan populations was minimal. Maximum likelihood trees based on <em>COI</em> and <em>Cytb</em> sequences strongly supported a close phylogenetic relationship between the northern Tianshan and Altai marmots, which clustered together, while the southern Tianshan population formed a separate clade. The <em>D-loop</em> region provided lower phylogenetic resolution. Based on these results, we confirm that the marmots in the Altai Mountains belong to <em>M. baibacina</em> and classify this plague focus as a <em>M. baibacina</em>–<em>Spermophilus undulatus</em> focus, given that <em>S. undulatus</em> is also a documented reservoir host in the area. These findings provide a molecular basis for targeted plague surveillance and control. The close genetic affinity between the northern Tianshan and Altai populations further suggests they may represent the same subspecies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"46 ","pages":"Article 102539"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of daily phase relations identified by multiomic analyses in acute pancreatitis.","authors":"Heather Waddell, Xiaozhong Zheng, Lucile Neyton, Tyler J Stevenson, Natalia Bochkina, Damian J Mole","doi":"10.1016/j.bbrep.2026.102533","DOIUrl":"https://doi.org/10.1016/j.bbrep.2026.102533","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is sudden inflammation of the pancreas which can cause organ failure and death, and with no targeted therapies in the clinic, there is an imperative to identify new potential avenues for therapeutics discovery. This exploratory study investigates the potential role of circadian rhythms in AP pathogenesis. We integrated and analysed multiomics data, including transcriptomics, metabolomics, and clinical laboratory measurements, synthesised from peripheral whole blood samples obtained from AP patients. Our exploratory findings identified a potential association between circadian rhythm dysregulation and disease severity. Specifically, we observed that the rhythmic expression of circadian genes across a 24-h period, such as the circadian locomotor output cycles kaput (<i>CLOCK</i>) and the brain and muscle ARNT-Like 1 (<i>BMAL1</i>) gene, and a specific subset of metabolites may be altered in AP. These exploratory results provide a foundation for future investigations into the potential therapeutic implications of targeting circadian rhythms in AP. Additional studies are required to validate these findings and to elucidate the specific mechanisms involved.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"102533"},"PeriodicalIF":2.2,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronan induces ERK activation with minimal transcriptomic changes in pancreatic α-cells.","authors":"Suguru Sonoyama, Akiko Mizokami, Tomomi Sano, Eijiro Jimi, Masafumi Moriyama, Takashi Kanematsu","doi":"10.1016/j.bbrep.2026.102525","DOIUrl":"https://doi.org/10.1016/j.bbrep.2026.102525","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is driven by the immune-mediated destruction of pancreatic β-cells. While β-cells are selectively targeted and depleted in T1D, α-cells that secrete glucagon are relatively spared from this autoimmune attack. Hyaluronan (HA), a glycosaminoglycan component of the extracellular matrix, accumulates within pancreatic islets in patients with T1D and in animal models, and has been implicated in promoting chronic inflammation. Given that surviving α-cells reside within this HA-rich microenvironment, we investigated whether HA contributes to molecular alterations in α-cells associated with the T1D phenotype. A murine α-cell line, αTC1-6, was stimulated with low-molecular-weight HA, which induced sustained extracellular signal-regulated kinase (ERK) phosphorylation upon HA stimulation, indicating activation of intracellular signaling. To assess whether this signaling response was accompanied by transcriptional changes, RNA sequencing was performed, and the resulting profile was compared with publicly available RNA-seq datasets from α-cells isolated from T1D donors. Despite robust ERK activation, HA stimulation elicited only minimal transcriptional changes relative to the T1D α-cell transcriptome. Gene set enrichment analysis further revealed a modest shift toward reduced peroxisome proliferator-activated receptor (PPAR) signaling in both HA-stimulated and T1D α-cells, suggesting a shared pathway-level signature. These findings indicate that HA alone does not fully recapitulate the extensive transcriptional remodeling observed in T1D α-cells, and that additional inflammatory or microenvironmental cues are required.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"102525"},"PeriodicalIF":2.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA GAS5 regulates osteogenic differentiation of human periodontal ligament stem cells through miR-23b-3p/STAT5B axis.","authors":"Qiufang Zhang, Yan Huang, Liping Huang, Zhisheng Zhang, Qiliang Zuo","doi":"10.1016/j.bbrep.2026.102516","DOIUrl":"https://doi.org/10.1016/j.bbrep.2026.102516","url":null,"abstract":"<p><p>Periodontal ligament stem cells (PDLSCs) play a crucial role in alveolar bone regeneration due to their inherent osteogenic differentiation capacity. However, the molecular mechanisms regulating PDLSC osteogenic differentiation remain incompletely understood. In this study, human PDLSCs were isolated and characterized, revealing that the cytoplasmic long non-coding RNA GAS5 was significantly upregulated during osteogenic induction. Functional assays demonstrated that GAS5 overexpression markedly enhanced alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of osteogenic marker genes (RUNX2, OCN, OPN). Conversely, GAS5 knockdown attenuated these osteogenic phenotypes. Mechanistically, GAS5 functioned as a competitive endogenous RNA (ceRNA) by directly binding to miR-23b-3p, thereby preventing miR-23b-3p-mediated post-transcriptional silencing of its target gene STAT5B. Rescue experiments confirmed that STAT5B silencing abolished the pro-osteogenic effects induced by GAS5 overexpression, while miR-23b-3p inhibition reversed the osteogenic impairment caused by GAS5 knockdown. Collectively, our findings reveal a novel regulatory axis (GAS5/miR-23b-3p/STAT5B) that modulates PDLSC osteogenic differentiation, offering a potential therapeutic target for periodontal tissue regeneration strategies.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"102516"},"PeriodicalIF":2.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic modulation of N6-methyladenosine by ionizing radiation in human cells.","authors":"L Cruz-Garcia, Philip Davies, Veronika Goriacha, Mustafa Najim, Stanislav Polozov, Maria Polozova, Christophe Badie","doi":"10.1016/j.bbrep.2026.102528","DOIUrl":"https://doi.org/10.1016/j.bbrep.2026.102528","url":null,"abstract":"<p><p>A cell's transcriptome is regulated through the integration of external and internal signals that activate intracellular signal pathways, epigenetic modifications and post-translational changes. Post-transcriptional regulation through RNA methylation has emerged as an important mechanism in cancer development, and informative for diagnosis and treatment. The most abundant one, N6-methyladenosine (m⁶A), regulates gene expression in eukaryotes. In the present study m⁶A RNA modifications have been characterized in response to ionizing radiation (IR) exposure in the HT1080 human cell line. Cells were exposed to a dose of 10 Gy of X-rays and harvested 1, 2, 10 min, 1 and 24 h after exposure. m⁶A sites were identified using long read nanopore direct RNA sequencing. A pipeline was designed using m6Anet to estimate m⁶A stoichiometries transcriptome-wide, which were then analysed by a beta-binomial regression model with moderated dispersion estimates and independent filtering to detect differentially methylated (DM) sites between treated and control samples. We found that IR modifies m⁶A sites in a dynamic way, inducing site specific increase of methylation. Remarkably, it peaks within the first minute after exposure, followed by a sharp decrease at 1 h without returning to baseline, increasing again after 24 h. Two transcripts of the nuclear encoded gene UQCR10, a subunit of the respiratory chain protein, sharing the same site presented a stable hypermethylation over time, confirmed by a modified quantitative PCR assay. Moreover, we generated Knockouts (KO) cell lines for 3 key enzymes involved in m⁶A methylation, a writer, a reader and an eraser namely METTL3, YTHDF2 and FTO, to better understand mechanistically IR driven m⁶A dynamics. Importantly, all three KOs presented a transcriptome wide decrease in RNA methylation following IR exposure. Lastly, m⁶A modifications were also confirmed in human skin biopsies exposed to IR, with the UQCR10 gene site also hypermethylated 24 h after a lower 2 Gy X-rays dose. To summarise, we provide evidence that IR modulates RNA m⁶A levels in a site-specific and dynamic way, with DM sites enriched in genes involved in bioenergetics, cell signalling/migration and apoptosis pathways, thus representing a rapid cellular response to radiation. Considering the essential role of m⁶A in controlling gene expression and physiological activities, this study established the basis for further studies assessing IR driving m⁶A with a potential role in radiation oncology and protection.</p>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"102528"},"PeriodicalIF":2.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}