Hybridalactone, agardhilactone, ecklonialactones, eiseniachlorides, and egregiachlorides, isolated from the marine macroalgae such as Laurencia hybrida, Agardhiella subulate, Ecklonia stolonifera, Eisenia bicyclis, and Egregia menziesii, are biosynthesized through a lipoxygenase (LOX)-mediated oxidative pathway involving polyunsaturated fatty acids (PUFAs). This enzymatic process generates hydroperoxide intermediates, which subsequently undergo regio- and stereospecific transformations to yield structurally diverse oxygenated metabolites, including plasmodiophorols and ectocarpins. These compounds are characterized by a conserved vinylcyclopentyl moiety, a structural hallmark critical to elucidating the mechanistic underpinnings of oxylipin biosynthesis in marine algae. The elucidation of these biosynthetic pathways enhances understanding of oxylipin enzymatic regulation and chemical diversity, while underscoring their ecological roles as signaling or defense molecules in marine ecosystems. Their unique structures and bioactivities offer potential for pharmacological and biotechnological applications, including novel bioactive agents. Investigating their production, structural complexity, and functionality is crucial for advancing marine natural product chemistry and exploring their ecological and industrial significance.
{"title":"The vinyl-α-substituted cyclopentyl oxylipins","authors":"Priyanka Kataria, Alexandre Guy, Thierry Durand, Camille Oger","doi":"10.1016/j.biochi.2025.07.004","DOIUrl":"10.1016/j.biochi.2025.07.004","url":null,"abstract":"<div><div>Hybridalactone, agardhilactone, ecklonialactones, eiseniachlorides, and egregiachlorides, isolated from the marine macroalgae such as <em>Laurencia hybrida</em>, <em>Agardhiella subulate, Ecklonia stolonifera</em>, <em>Eisenia bicyclis</em>, and <em>Egregia menziesii</em>, are biosynthesized through a lipoxygenase (LOX)-mediated oxidative pathway involving polyunsaturated fatty acids (PUFAs). This enzymatic process generates hydroperoxide intermediates, which subsequently undergo regio- and stereospecific transformations to yield structurally diverse oxygenated metabolites, including plasmodiophorols and ectocarpins. These compounds are characterized by a conserved vinylcyclopentyl moiety, a structural hallmark critical to elucidating the mechanistic underpinnings of oxylipin biosynthesis in marine algae. The elucidation of these biosynthetic pathways enhances understanding of oxylipin enzymatic regulation and chemical diversity, while underscoring their ecological roles as signaling or defense molecules in marine ecosystems. Their unique structures and bioactivities offer potential for pharmacological and biotechnological applications, including novel bioactive agents. Investigating their production, structural complexity, and functionality is crucial for advancing marine natural product chemistry and exploring their ecological and industrial significance.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 41-50"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-18DOI: 10.1016/j.biochi.2025.09.010
Maureen Gerlei, Louis Pruvost, Michel Linder
This study compares salmon heads and krill as natural marine sources of omega-3-rich phospholipids for liposome formulation, serving as potential carriers of bioactive compounds in nutrition and preventive health. Salmon and krill oil obtained by green processes, yielded lipid fractions enriched in both neutral and polar lipids, containing esterified long-chain polyunsaturated fatty acids (LC-PUFAs) such as EPA and DHA. The triacylglycerol/polar lipid ratios were 0.71 for salmon and 0.39 for krill, with significant differences in lipid class distribution and phospholipid concentrations, determined via acetone fractionation. Polar fractions exhibited high LC-PUFA content: 5.36 % EPA and 13.90 % DHA respectively for salmon, whereas polar lipids in krill contained 12.96 % EPA and 7.26 % DHA. Nutritional and health-related indices including atherogenicity, thrombogenicity, polyene, health-promoting, oxidisability, peroxidisability, and hypo/hypercholesterolemic ratios, highlighted the specific advantages and limitations of each source. The relative proportions of fatty acids influenced the physicochemical properties of the resulting liposomes. Dynamic Light Scattering and Nanoparticle Tracking Analysis revealed particle sizes of ∼86.56 nm for salmon and 176.22 nm for krill liposomes, with highly negative zeta potentials ensuring long-term colloidal stability. Both liposome types showed good size homogeneity, low polydispersity indices (∼0.2), and favorable particle mobility under imaging. Overall, these marine by-products represent sustainable sources of polar lipids naturally enriched in EPA, DHA and astaxanthin, the main carotenoid present with well-documented antioxidant properties, providing functional and nutritional benefits. This highlights their significant potential for the development of lipid-based delivery systems in food, nutraceutical and health applications.
{"title":"Salmon and krill phospholipids: Two nanocarriers with interesting physico-chemical properties","authors":"Maureen Gerlei, Louis Pruvost, Michel Linder","doi":"10.1016/j.biochi.2025.09.010","DOIUrl":"10.1016/j.biochi.2025.09.010","url":null,"abstract":"<div><div>This study compares salmon heads and krill as natural marine sources of omega-3-rich phospholipids for liposome formulation, serving as potential carriers of bioactive compounds in nutrition and preventive health. Salmon and krill oil obtained by green processes, yielded lipid fractions enriched in both neutral and polar lipids, containing esterified long-chain polyunsaturated fatty acids (LC-PUFAs) such as EPA and DHA. The triacylglycerol/polar lipid ratios were 0.71 for salmon and 0.39 for krill, with significant differences in lipid class distribution and phospholipid concentrations, determined via acetone fractionation. Polar fractions exhibited high LC-PUFA content: 5.36 % EPA and 13.90 % DHA respectively for salmon, whereas polar lipids in krill contained 12.96 % EPA and 7.26 % DHA. Nutritional and health-related indices including atherogenicity, thrombogenicity, polyene, health-promoting, oxidisability, peroxidisability, and hypo/hypercholesterolemic ratios, highlighted the specific advantages and limitations of each source. The relative proportions of fatty acids influenced the physicochemical properties of the resulting liposomes. Dynamic Light Scattering and Nanoparticle Tracking Analysis revealed particle sizes of ∼86.56 nm for salmon and 176.22 nm for krill liposomes, with highly negative zeta potentials ensuring long-term colloidal stability. Both liposome types showed good size homogeneity, low polydispersity indices (∼0.2), and favorable particle mobility under imaging. Overall, these marine by-products represent sustainable sources of polar lipids naturally enriched in EPA, DHA and astaxanthin, the main carotenoid present with well-documented antioxidant properties, providing functional and nutritional benefits. This highlights their significant potential for the development of lipid-based delivery systems in food, nutraceutical and health applications.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 19-29"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-02DOI: 10.1016/j.biochi.2025.08.019
M. Miklaszewska , R.E. Gomez , P. Van Delft , M. Le Guédard , C. Chambaud , C. Mirande-Bret , L. Fouillen , F. Corellou , F. Domergue
Marine microalgae are the primary producers of important lipids in oceanic ecosystems. In particular, they sustain the food web with omega-3 very-long-chain polyunsaturated fatty acids (n-3 PUFAs), which play a protective role against various human metabolic disorders and are thus considered highly beneficial to health. Ostreococcus tauri is a marine pico-eukaryote that contains high levels of several n-3 PUFAs, including docosahexaenoic acid (22:6n3; DHA), octadecapentaenoic acid (18:5n3, OPA), and hexadecatetraenoic acid (16:4n3), each with a distinct distribution. While DHA and OPA are restricted to microsomal and plastidial lipids, respectively, 16:4n3 is found in galactolipids as well as in betaine and neutral lipids. The genome of O. tauri contains 14 genes encoding fatty acid desaturases. In this study, we characterized the enzyme encoded by OT_ostta13g01550 (Ot13bDES) as a plastidial cytochrome b5-fused delta-4 desaturase involved in 16:4n3 biosynthesis. Transient heterologous expression of Ot13bDES in Nicotiana benthamiana led to the production of 16:4n3 and 16:3n6, but failed to produce 18:5n3 when Ot13bDES was coexpressed with plastidial Δ6-desaturases, suggesting Ot13bDES has a strict Δ4 regioselectivity. Lipidomic analyses of stable transgenic Arabidopsis lines further showed a nearly 100 % conversion rate of 16:3n3 to 16:4n3 in the best-performing lines, demonstrating that Ot13bDES has a very high catalytic activity. Additionally, 16:4n3 was predominantly localized to monogalactosyldiacylglycerol (MGDG). This study provides the first functional characterization of a plastidial cytochrome b5-fused delta-4 desaturase through heterologous expression in higher plants.
{"title":"Functional characterization of a plastidial cytochrome b5-fused Δ4-desaturase from Ostreococcus tauri in higher plants","authors":"M. Miklaszewska , R.E. Gomez , P. Van Delft , M. Le Guédard , C. Chambaud , C. Mirande-Bret , L. Fouillen , F. Corellou , F. Domergue","doi":"10.1016/j.biochi.2025.08.019","DOIUrl":"10.1016/j.biochi.2025.08.019","url":null,"abstract":"<div><div>Marine microalgae are the primary producers of important lipids in oceanic ecosystems. In particular, they sustain the food web with omega-3 very-long-chain polyunsaturated fatty acids (n-3 PUFAs), which play a protective role against various human metabolic disorders and are thus considered highly beneficial to health. <em>Ostreococcus tauri</em> is a marine pico-eukaryote that contains high levels of several n-3 PUFAs, including docosahexaenoic acid (22:6n3; DHA), octadecapentaenoic acid (18:5n3, OPA), and hexadecatetraenoic acid (16:4n3), each with a distinct distribution. While DHA and OPA are restricted to microsomal and plastidial lipids, respectively, 16:4n3 is found in galactolipids as well as in betaine and neutral lipids. The genome of <em>O. tauri</em> contains 14 genes encoding fatty acid desaturases. In this study, we characterized the enzyme encoded by <em>OT_ostta13g01550</em> (<em>Ot13bDES</em>) as a plastidial cytochrome <em>b</em>5-fused delta-4 desaturase involved in 16:4n3 biosynthesis. Transient heterologous expression of <em>Ot13bDES</em> in <em>Nicotiana benthamiana</em> led to the production of 16:4n3 and 16:3n6, but failed to produce 18:5n3 when <em>Ot13bDES</em> was coexpressed with plastidial Δ6-desaturases, suggesting Ot13bDES has a strict Δ4 regioselectivity. Lipidomic analyses of stable transgenic Arabidopsis lines further showed a nearly 100 % conversion rate of 16:3n3 to 16:4n3 in the best-performing lines, demonstrating that Ot13bDES has a very high catalytic activity. Additionally, 16:4n3 was predominantly localized to monogalactosyldiacylglycerol (MGDG). This study provides the first functional characterization of a plastidial cytochrome <em>b</em>5-fused delta-4 desaturase through heterologous expression in higher plants.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 73-85"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-09DOI: 10.1016/j.biochi.2025.07.005
Mickaël Péron , Philippe Soudant , Fabienne Le Grand , David Mazurais , Victor Simon , Christel Lefrançois , Marie Vagner
Long-chain polyunsaturated fatty acids (LC PUFA), particularly docosahexaenoic acid (DHA), are essential for cell membrane structure and function, impacting overall fish performance. These molecules, produced primarily by phytoplankton, are transferred up the trophic chain; however, climate change is predicted to modify phytoplankton communities with a cascading effect on the global DHA production and thus availability for consumers such as fish. This study aimed to evaluate the effects of dietary DHA limitation on i) the fatty acid composition in fish tissues ii) somatic growth, swimming performance, and metabolic rates, and iii) the activation of biosynthetic pathways at the molecular level, by measuring gene expression involved in DHA synthesis. We conditioned wild-caught European sea bass (Dicentrarchus labrax) juveniles for five months on a DHA-depleted or control diet. Dietary DHA limitation led to selective retention or synthesis of DHA in fish tissues (liver, brain, and muscle), a reduced growth and an up-regulation of DHA biosynthetic pathways without compensating for DHA deficiency in tissues. Fish fed the low DHA diet may have up-regulated biosynthetic pathway which may be energetically costly, as high tissue DHA correlated with reduced growth. Alternatively, the lower tissue DHA levels in these fish might cause slower growth. However, metabolic rates and swimming performance were not affected by dietary treatment. Inter-individual variability was observed across all variables, highlighting underlying trade-offs when facing DHA limitation. This work provides insight into the physiological consequences of dietary DHA reduction due to global change and the mechanisms fish employ to mitigate its effects.
{"title":"Dietary DHA limitation did not affect swimming and metabolic performance, but reduced growth in wild European sea bass","authors":"Mickaël Péron , Philippe Soudant , Fabienne Le Grand , David Mazurais , Victor Simon , Christel Lefrançois , Marie Vagner","doi":"10.1016/j.biochi.2025.07.005","DOIUrl":"10.1016/j.biochi.2025.07.005","url":null,"abstract":"<div><div>Long-chain polyunsaturated fatty acids (LC PUFA), particularly docosahexaenoic acid (DHA), are essential for cell membrane structure and function, impacting overall fish performance. These molecules, produced primarily by phytoplankton, are transferred up the trophic chain; however, climate change is predicted to modify phytoplankton communities with a cascading effect on the global DHA production and thus availability for consumers such as fish. This study aimed to evaluate the effects of dietary DHA limitation on i) the fatty acid composition in fish tissues ii) somatic growth, swimming performance, and metabolic rates, and iii) the activation of biosynthetic pathways at the molecular level, by measuring gene expression involved in DHA synthesis. We conditioned wild-caught European sea bass (<em>Dicentrarchus labrax</em>) juveniles for five months on a DHA-depleted or control diet. Dietary DHA limitation led to selective retention or synthesis of DHA in fish tissues (liver, brain, and muscle), a reduced growth and an up-regulation of DHA biosynthetic pathways without compensating for DHA deficiency in tissues. Fish fed the low DHA diet may have up-regulated biosynthetic pathway which may be energetically costly, as high tissue DHA correlated with reduced growth. Alternatively, the lower tissue DHA levels in these fish might cause slower growth. However, metabolic rates and swimming performance were not affected by dietary treatment. Inter-individual variability was observed across all variables, highlighting underlying trade-offs when facing DHA limitation. This work provides insight into the physiological consequences of dietary DHA reduction due to global change and the mechanisms fish employ to mitigate its effects.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 60-72"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.biochi.2025.10.007
Ravy Leon Foun Lin, Adam Bellaiche, Catherine Etchebest
Despite its relevance, the well-known paradigm that connects sequence, structure and function still overlooks an important factor: the dynamics of the proteins involved in functional mechanisms. Experimental techniques such as nuclear magnetic resonance and, more recently, cryo-electron microscopy, provide some insight into the conformational diversity of a protein. However, technical difficulties limit their application to the proteome scale. Nevertheless, computational methods are now considered efficient in providing valuable information about the dynamical landscape of a given protein, thereby improving our understanding of its function. Among these methods, molecular dynamics simulations have become very popular and generate a large amount of data that can now be used by Artificial Intelligence approaches for prediction. This paper will describe and discuss the concepts and a few applications of these approaches.
{"title":"The key role of the dynamics and flexibility of proteins in functional mechanisms: How computational methods can contribute to their identification","authors":"Ravy Leon Foun Lin, Adam Bellaiche, Catherine Etchebest","doi":"10.1016/j.biochi.2025.10.007","DOIUrl":"10.1016/j.biochi.2025.10.007","url":null,"abstract":"<div><div>Despite its relevance, the well-known paradigm that connects sequence, structure and function still overlooks an important factor: the dynamics of the proteins involved in functional mechanisms. Experimental techniques such as nuclear magnetic resonance and, more recently, cryo-electron microscopy, provide some insight into the conformational diversity of a protein. However, technical difficulties limit their application to the proteome scale. Nevertheless, computational methods are now considered efficient in providing valuable information about the dynamical landscape of a given protein, thereby improving our understanding of its function. Among these methods, molecular dynamics simulations have become very popular and generate a large amount of data that can now be used by Artificial Intelligence approaches for prediction. This paper will describe and discuss the concepts and a few applications of these approaches.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 8-26"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-26DOI: 10.1016/j.biochi.2025.09.014
Jacques Delarue
This review aims to provide a comprehensive overview of the available data on the effects of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) on insulin resistance (IR) associated with non-communicable diseases (NCDs), including obesity and type 2 diabetes. In recent years, inflammation of adipose tissue (AT) has emerged as a pivotal contributor to IR in these NCDs. Basic studies conducted on isolated adipocytes and rodents consistently demonstrate that LC n-3 PUFAs attenuate AT inflammation through multiple mechanisms. Furthermore, rodent studies have shown that even low doses of LC n-3 PUFAs can effectively prevent IR, particularly when induced by a high-fat diet (HFD). However, trials conducted in humans, using primarily hyperinsulinemic clamp methods, have yielded more varied results, with several studies indicating a sensitising effect on liver and, occasionally, muscle (as assessed by plasma glucose utilisation). In patients with polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic dysfunction-associated steatohepatitis (MASLD), LC n-3 PUFAs have been observed to decrease IR, as measured by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) score. In contrast, most meta-analyses of studies conducted in patients with type 2 diabetes (T2D) have concluded to the inefficacy of LC n-3 PUFAs in reducing IR. However, several meta-analyses have identified a protective effect of LC n-3 PUFAs against T2D in Asians, with no heterogeneity observed, contrasting the findings in Western populations, where heterogeneity exists. The most recent analysis and the large UK Biobank cohort have concluded to a protective effect of LC n-3 PUFAs. Therefore, it can be proposed that LC n-3 PUFAs should be administered to individuals with NCD-associated IR and at high risk of T2D, in conjunction with a healthy diet, such as the Mediterranean diet.
{"title":"Beneficial effects of long-chain n-3 fatty acids on insulin-resistance: basic and clinical aspects","authors":"Jacques Delarue","doi":"10.1016/j.biochi.2025.09.014","DOIUrl":"10.1016/j.biochi.2025.09.014","url":null,"abstract":"<div><div>This review aims to provide a comprehensive overview of the available data on the effects of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) on insulin resistance (IR) associated with non-communicable diseases (NCDs), including obesity and type 2 diabetes. In recent years, inflammation of adipose tissue (AT) has emerged as a pivotal contributor to IR in these NCDs. Basic studies conducted on isolated adipocytes and rodents consistently demonstrate that LC n-3 PUFAs attenuate AT inflammation through multiple mechanisms. Furthermore, rodent studies have shown that even low doses of LC n-3 PUFAs can effectively prevent IR, particularly when induced by a high-fat diet (HFD). However, trials conducted in humans, using primarily hyperinsulinemic clamp methods, have yielded more varied results, with several studies indicating a sensitising effect on liver and, occasionally, muscle (as assessed by plasma glucose utilisation). In patients with polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic dysfunction-associated steatohepatitis (MASLD), LC n-3 PUFAs have been observed to decrease IR, as measured by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) score. In contrast, most meta-analyses of studies conducted in patients with type 2 diabetes (T2D) have concluded to the inefficacy of LC n-3 PUFAs in reducing IR. However, several meta-analyses have identified a protective effect of LC n-3 PUFAs against T2D in Asians, with no heterogeneity observed, contrasting the findings in Western populations, where heterogeneity exists. The most recent analysis and the large UK Biobank cohort have concluded to a protective effect of LC n-3 PUFAs. Therefore, it can be proposed that LC n-3 PUFAs should be administered to individuals with NCD-associated IR and at high risk of T2D, in conjunction with a healthy diet, such as the Mediterranean diet.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 30-40"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-11DOI: 10.1016/j.biochi.2025.09.006
Jiye Fu , Tianyu Chen , Na Lu , Xuan Pan , Jing Tu
Guanine-rich sequences are widely distributed throughout the human genome and are capable of forming intramolecular G-quadruplex (G4) structures through Hoogsteen hydrogen bonding. These structures have been implicated in diverse regulatory processes. While extensive studies have established that loop architecture—particularly loop length and composition—profoundly affects G4 structural stability, most investigations have relied on synthetic sequences with predefined loop configurations that do not accurately reflect genomic contexts. In the current study, we analyzed the chain composition and stability of G-quadruplexes within the human genome to clarify the relationship between them by high throughput sequencing data. We utilized G4-forming sequences identified by G4-seq and G4-miner—two sequencing-based methods that detect G4s through polymerase stalling–associated drops in sequencing quality scores, where more stable structures produce stronger signals and thus higher detection rates—as the primary dataset. Our analysis revealed a negative correlation between total loop length and G4 stability, whereas individual loop length distributions exhibited minimal influence. Interestingly, G4s with short loops frequently occur in the genome as microsatellites or tandem atypical G4 arrays, resulting in structural stability profiles that deviate from those observed in synthetic G4 motifs in vitro. Molecular dynamics simulations incorporating native flanking sequences further corroborated these findings, underscoring the importance of genomic context in determining G4 stability. We note that the research was restricted to canonical G4s, which may limit the generality of our conclusions.
{"title":"Decoding G-quadruplex stability: the role of loop architecture and sequence context in the human genome","authors":"Jiye Fu , Tianyu Chen , Na Lu , Xuan Pan , Jing Tu","doi":"10.1016/j.biochi.2025.09.006","DOIUrl":"10.1016/j.biochi.2025.09.006","url":null,"abstract":"<div><div>Guanine-rich sequences are widely distributed throughout the human genome and are capable of forming intramolecular G-quadruplex (G4) structures through Hoogsteen hydrogen bonding. These structures have been implicated in diverse regulatory processes. While extensive studies have established that loop architecture—particularly loop length and composition—profoundly affects G4 structural stability, most investigations have relied on synthetic sequences with predefined loop configurations that do not accurately reflect genomic contexts. In the current study, we analyzed the chain composition and stability of G-quadruplexes within the human genome to clarify the relationship between them by high throughput sequencing data. We utilized G4-forming sequences identified by G4-seq and G4-miner—two sequencing-based methods that detect G4s through polymerase stalling–associated drops in sequencing quality scores, where more stable structures produce stronger signals and thus higher detection rates—as the primary dataset. Our analysis revealed a negative correlation between total loop length and G4 stability, whereas individual loop length distributions exhibited minimal influence. Interestingly, G4s with short loops frequently occur in the genome as microsatellites or tandem atypical G4 arrays, resulting in structural stability profiles that deviate from those observed in synthetic G4 motifs in vitro. Molecular dynamics simulations incorporating native flanking sequences further corroborated these findings, underscoring the importance of genomic context in determining G4 stability. We note that the research was restricted to canonical G4s, which may limit the generality of our conclusions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 236-243"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hybrid internal-terminal exons function as either internal or terminal exons. Their evolutionary origins remain unclear. Here, we investigate the phylogenetic origin and regulation of a hybrid exon, 9A9′, in the TPM1 gene encoding tropomyosin alpha-1. We demonstrate that exon 9A9′ was originally terminal in non-vertebrate deuterostomes and switched to internal in vertebrates through the exonization of a downstream exon, 9B. While the terminal nature of exon 9A9′ was lost in most vertebrates, it was conserved in amphibians and coelacanths where it behaves as a hybrid internal-terminal exon. Using Xenopus laevis as a model, we show that the preservation of terminal exon 9A9′ in the tpm1 gene likely arose from evolutionary pressures to mitigate the developmental toxicity linked to exon 9B inclusion during neurulation. We identify two peculiarities of terminal exon 9A9': it lies downstream of an AG-independent intron, and its definition is supported by an intronic cis-regulatory element, the UTE, which enhances recognition of the weak cleavage-polyadenylation site. Our findings characterize the molecular mechanisms underlying the regulation of hybrid internal-terminal exons and reveal how evolutionary pressures can reactivate vestigial traits to resolve developmental challenges. This work broadens our understanding of alternative splicing evolution and its significance in vertebrate development.
{"title":"Insights into the evolution and regulation of hybrid internal-terminal exons from tropomyosin exon 9A in Xenopus laevis","authors":"Agnès Méreau, Hubert Lerivray, Justine Viet, Serge Hardy, Luc Paillard , Yann Audic","doi":"10.1016/j.biochi.2025.07.009","DOIUrl":"10.1016/j.biochi.2025.07.009","url":null,"abstract":"<div><div>Hybrid internal-terminal exons function as either internal or terminal exons. Their evolutionary origins remain unclear. Here, we investigate the phylogenetic origin and regulation of a hybrid exon, 9A9′, in the <em>TPM1</em> gene encoding tropomyosin alpha-1. We demonstrate that exon 9A9′ was originally terminal in non-vertebrate deuterostomes and switched to internal in vertebrates through the exonization of a downstream exon, 9B. While the terminal nature of exon 9A9′ was lost in most vertebrates, it was conserved in amphibians and coelacanths where it behaves as a hybrid internal-terminal exon. Using <em>Xenopus laevis</em> as a model, we show that the preservation of terminal exon 9A9′ in the <em>tpm1</em> gene likely arose from evolutionary pressures to mitigate the developmental toxicity linked to exon 9B inclusion during neurulation. We identify two peculiarities of terminal exon 9A9': it lies downstream of an AG-independent intron, and its definition is supported by an intronic <em>cis</em>-regulatory element, the UTE, which enhances recognition of the weak cleavage-polyadenylation site. Our findings characterize the molecular mechanisms underlying the regulation of hybrid internal-terminal exons and reveal how evolutionary pressures can reactivate vestigial traits to resolve developmental challenges. This work broadens our understanding of alternative splicing evolution and its significance in vertebrate development.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"238 ","pages":"Pages 29-42"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-05-12DOI: 10.1016/j.biochi.2025.05.003
Oriana Puidebat, Sylvain Egloff
Cyclin-Dependent Kinase 9 (CDK9) is a critical regulator of transcriptional elongation, functioning within the Positive Transcription Elongation Factor b (P-TEFb) complex alongside Cyclin T1. P-TEFb facilitates the release of RNA polymerase II (RNAPII) from promoter-proximal pausing, thereby enabling productive transcriptional elongation. CDK9 activity is tightly controlled by the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, comprising 7SK snRNA, LARP7, MEPCE, and HEXIM1/2. Under homeostatic conditions, the 7SK snRNP sequesters and inactivates a fraction of P-TEFb, maintaining it in a repressed state. However, in response to cellular stress or increased transcriptional demand, P-TEFb is released from 7SK snRNP, activating CDK9 to ensure precise, context-dependent transcriptional control. This regulatory switch allows dynamic adaptation to environmental and intracellular cues. Emerging evidence implicates 7SK snRNP deregulation in cancer progression. This review explores the intricate interplay between 7SK snRNP and CDK9, highlighting how disruptions in individual 7SK snRNP components drive transcriptional imbalances, amplify oncogenic programs, and promote a tumorigenic environment.
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The emergence of antibiotic resistance has rendered the treatment of bacterial infections exceedingly challenging, with diseases caused by resistant strains often resulting in significant morbidity and mortality. Consequently, it is crucial to investigate the mechanisms underlying antibiotic resistance. Outer membrane vesicles (OMVs) are nanoscale spheres characterized by a double membrane structure, released by Gram-negative bacteria (GNB). While the mechanisms governing OMV biogenesis remain under investigation, three models have been proposed. These vesicles have been implicated in enhancing bacterial survival during antibiotic treatment and contributing to the onset and development of drug resistance through various pathways. OMVs function as a secretion system, delivering cargo that mediates intercellular communication to neighboring cells, and their closed structure facilitates this molecular delivery. Vesicles released into the extracellular compartment can protect bacteria from antibiotic treatment by promoting horizontal gene transfer, inactivating or binding antibiotics, influencing biofilm formation, and mediating bacterial gene mutations, among other mechanisms. Many studies have demonstrated that OMVs play a critical role during antibiotic exposure. An in-depth understanding of the mechanisms of OMVs in the development of bacterial drug resistance could help develop more effective therapeutic strategies to prevent persistent bacterial infections. This review focuses on summarising the latest evidence on the involvement of OMVs in the development of drug resistance, to provide ideas for future studies.
{"title":"Mechanisms of outer membrane vesicles in bacterial drug resistance: Insights and implications","authors":"Xianyu Zhang, Wenbo Ding, Jianyu Yang, Linran Gao, Qianying Wang, Jingjing Wang, Yu Luo, Xin Yuan, Baoyu Sun, Jifei Yang, Yujiao Zhou, Liyuan Sun","doi":"10.1016/j.biochi.2025.07.024","DOIUrl":"10.1016/j.biochi.2025.07.024","url":null,"abstract":"<div><div>The emergence of antibiotic resistance has rendered the treatment of bacterial infections exceedingly challenging, with diseases caused by resistant strains often resulting in significant morbidity and mortality. Consequently, it is crucial to investigate the mechanisms underlying antibiotic resistance. Outer membrane vesicles (OMVs) are nanoscale spheres characterized by a double membrane structure, released by Gram-negative bacteria (GNB). While the mechanisms governing OMV biogenesis remain under investigation, three models have been proposed. These vesicles have been implicated in enhancing bacterial survival during antibiotic treatment and contributing to the onset and development of drug resistance through various pathways. OMVs function as a secretion system, delivering cargo that mediates intercellular communication to neighboring cells, and their closed structure facilitates this molecular delivery. Vesicles released into the extracellular compartment can protect bacteria from antibiotic treatment by promoting horizontal gene transfer, inactivating or binding antibiotics, influencing biofilm formation, and mediating bacterial gene mutations, among other mechanisms. Many studies have demonstrated that OMVs play a critical role during antibiotic exposure. An in-depth understanding of the mechanisms of OMVs in the development of bacterial drug resistance could help develop more effective therapeutic strategies to prevent persistent bacterial infections. This review focuses on summarising the latest evidence on the involvement of OMVs in the development of drug resistance, to provide ideas for future studies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"238 ","pages":"Pages 77-90"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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