Metallomics最新文献_第5页

Novel binuclear copper(II) complexes with sulfanylpyrazole ligands: synthesis, crystal structure, fungicidal, cytostatic, and cytotoxic activity. 具有硫酰吡唑配体的新型双核铜（II）配合物：合成、晶体结构、杀菌、细胞抑制和细胞毒性活性。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-06-04 DOI: 10.1093/mtomcs/mfae024

Vnira R Akhmetova, Nail S Akhmadiev, Aidar T Gubaidullin, Aida I Samigullina, Andrey B Glazyrin, Rais A Sadykov, Diana V Ishmetova, Yulia V Vakhitova

引用次数: 0

Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach. 大鼠体内锌同位素的膳食和体内平衡控制：控制进食实验和建模方法。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-06-04 DOI: 10.1093/mtomcs/mfae026

Nicolas Bourgon, Théo Tacail, Klervia Jaouen, Jennifer N Leichliter, Jeremy McCormack, Daniela E Winkler, Marcus Clauss, Thomas Tütken

{"title":"Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach.","authors":"Nicolas Bourgon, Théo Tacail, Klervia Jaouen, Jennifer N Leichliter, Jeremy McCormack, Daniela E Winkler, Marcus Clauss, Thomas Tütken","doi":"10.1093/mtomcs/mfae026","DOIUrl":"10.1093/mtomcs/mfae026","url":null,"abstract":"The stable isotope composition of zinc (δ66Zn), which is an essential trace metal for many biological processes in vertebrates, is increasingly used in ecological, archeological, and paleontological studies to assess diet and trophic level discrimination among vertebrates. However, the limited understanding of dietary controls and isotopic fractionation processes on Zn isotope variability in animal tissues and biofluids limits precise dietary reconstructions. The current study systematically investigates the dietary effects on Zn isotope composition in consumers using a combined controlled feeding experiment and box-modeling approach. For this purpose, 21 rats were fed one of seven distinct animal- and plant-based diets and a total of 148 samples including soft and hard tissue, biofluid, and excreta samples of these individuals were measured for δ66Zn. Relatively constant Zn isotope fractionation is observed across the different dietary groups for each tissue type, implying that diet is the main factor controlling consumer tissue δ66Zn values, independent of diet composition. Furthermore, a systematic δ66Zn diet-enamel fractionation is reported for the first time, enabling diet reconstruction based on δ66Zn values from tooth enamel. In addition, we investigated the dynamics of Zn isotope variability in the body using a box-modeling approach, providing a model of Zn isotope homeostasis and inferring residence times, while also further supporting the hypothesis that δ66Zn values of vertebrate tissues are primarily determined by that of the diet. Altogether this provides a solid foundation for refined (paleo)dietary reconstruction using Zn isotopes of vertebrate tissues.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript. 草履虫暴露于镉的特异性阶段确定了独特的转录组反应级联和一种未表征的镉反应转录本。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae016

Norah Almutairi, Naema Khan, Alexandra Harrison-Smith, Volker M Arlt, Stephen R Stürzenbaum

{"title":"Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript.","authors":"Norah Almutairi, Naema Khan, Alexandra Harrison-Smith, Volker M Arlt, Stephen R Stürzenbaum","doi":"10.1093/mtomcs/mfae016","DOIUrl":"10.1093/mtomcs/mfae016","url":null,"abstract":"Age/stage sensitivity is considered a significant factor in toxicity assessments. Previous studies investigated cadmium (Cd) toxicosis in Caenorhabditis elegans, and a plethora of metal-responsive genes/proteins have been identified and characterized in fine detail; however, most of these studies neglected age sensitivity and stage-specific response to toxicants at the molecular level. This present study compared the transcriptome response between C. elegans L3 vs L4 larvae exposed to 20 µM Cd to explore the transcriptional hallmarks of stage sensitivity. The results showed that the transcriptome of the L3 stage, despite being exposed to Cd for a shorter period, was more affected than the L4 stage, as demonstrated by differences in transcriptional changes and magnitude of induction. Additionally, T08G5.1, a hitherto uncharacterized gene located upstream of metallothionein (mtl-2), was transcriptionally hyperresponsive to Cd exposure. Deletion of one or both metallothioneins (mtl-1 and/or mtl-2) increased T08G5.1 expression, suggesting that its expression is linked to the loss of metallothionein. The generation of an extrachromosomal transgene (PT08G5.1:: GFP) revealed that T08G5.1 is constitutively expressed in the head neurons and induced in gut cells upon Cd exposure, not unlike mtl-1 and mtl-2. The low abundance of cysteine residues in T08G5.1 suggests, however, that it may not be involved directly in Cd sequestration to limit its toxicity like metallothionein, but might be associated with a parallel pathway, possibly an oxidative stress response.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence. 利用同步加速器显微 X 射线荧光分析人脑组织中汞和硒的分布。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae018

Alexis N Webb, Olga Antipova, Serena Shughoury, Jose M Farfel, David A Bennett, Yansheng Du, Wei Zheng, Linda H Nie

{"title":"Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence.","authors":"Alexis N Webb, Olga Antipova, Serena Shughoury, Jose M Farfel, David A Bennett, Yansheng Du, Wei Zheng, Linda H Nie","doi":"10.1093/mtomcs/mfae018","DOIUrl":"10.1093/mtomcs/mfae018","url":null,"abstract":"Mercury is a well-recognized environmental contaminant and neurotoxin, having been associated with a number of deleterious neurological conditions including neurodegenerative diseases, such as Alzheimer's disease. To investigate how mercury and other metals behave in the brain, we used synchrotron micro-X-ray fluorescence to map the distribution pattern and quantify concentrations of metals in human brain. Brain tissue was provided by the Rush Alzheimer's Disease Center and samples originated from individuals diagnosed with Alzheimer's disease and without cognitive impairment. Data were collected at the 2-ID-E beamline at the Advanced Photon Source at Argonne National Laboratory with an incident beam energy of 13 keV. Course scans were performed at low resolution to determine gross tissue features, after which smaller regions were selected to image at higher resolution. The findings revealed (1) the existence of mercury particles in the brain samples of two subjects; (2) co-localization and linear correlation of mercury and selenium in all particles; (3) co-localization of these particles with zinc structures; and (4) association with sulfur in some of these particles. These results suggest that selenium and sulfur may play protective roles against mercury in the brain, potentially binding with the metal to reduce the induced toxicity, although at different affinities. Our findings call for further studies to investigate the relationship between mercury, selenium, and sulfur, as well as the potential implications in Alzheimer's disease and related dementias.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"16 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11064728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro. 甘氨酰-L-组氨酰-L-赖氨酸（GHK）可在体外防止铜和锌诱导的蛋白质聚集和中枢神经系统细胞死亡。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae019

Jin-Hong Min, Heela Sarlus, Robert A Harris

{"title":"Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.","authors":"Jin-Hong Min, Heela Sarlus, Robert A Harris","doi":"10.1093/mtomcs/mfae019","DOIUrl":"10.1093/mtomcs/mfae019","url":null,"abstract":"Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species. 探索具有高催化活性的稳定铜配体复合物，以产生 ROS。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae020

Merwan Bouraguba, Adeline M Schmitt, Venkata Suseela Yelisetty, Bertrand Vileno, Frédéric Melin, Elise Glattard, Christophe Orvain, Vincent Lebrun, Laurent Raibaut, Marianne Ilbert, Burkhard Bechinger, Petra Hellwig, Christian Gaiddon, Angélique Sour, Peter Faller

{"title":"Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species.","authors":"Merwan Bouraguba, Adeline M Schmitt, Venkata Suseela Yelisetty, Bertrand Vileno, Frédéric Melin, Elise Glattard, Christophe Orvain, Vincent Lebrun, Laurent Raibaut, Marianne Ilbert, Burkhard Bechinger, Petra Hellwig, Christian Gaiddon, Angélique Sour, Peter Faller","doi":"10.1093/mtomcs/mfae020","DOIUrl":"10.1093/mtomcs/mfae020","url":null,"abstract":"Metal ion-catalyzed overproduction of reactive oxygen species (ROS) is believed to contribute significantly to oxidative stress and be involved in several biological processes, from immune defense to development of diseases. Among the essential metal ions, copper is one of the most efficient catalysts in ROS production in the presence of O2 and a physiological reducing agent such as ascorbate. To control this chemistry, Cu ions are tightly coordinated to biomolecules. Free or loosely bound Cu ions are generally avoided to prevent their toxicity. In the present report, we aim to find stable Cu-ligand complexes (Cu-L) that can efficiently catalyze the production of ROS in the presence of ascorbate under aerobic conditions. Thermodynamic stability would be needed to avoid dissociation in the biological environment, and high ROS catalysis is of interest for applications as antimicrobial or anticancer agents. A series of Cu complexes with the well-known tripodal and tetradentate ligands containing a central amine linked to three pyridyl-alkyl arms of different lengths were investigated. Two of them with mixed arm length showed a higher catalytic activity in the oxidation of ascorbate and subsequent ROS production than Cu salts in buffer, which is an unprecedented result. Despite these high catalytic activities, no increased antimicrobial activity toward Escherichia coli or cytotoxicity against eukaryotic AGS cells in culture related to Cu-L-based ROS production could be observed. The potential reasons for discrepancy between in vitro and in cell data are discussed.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848346","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}

引用次数: 0

Impact of aging on copper isotopic composition in the murine brain. 衰老对鼠脑中铜同位素组成的影响

IF 2.9 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae008

Esther Lahoud, Frédéric Moynier, Tu-Han Luu, Brandon Mahan, Marie Le Borgne

{"title":"Impact of aging on copper isotopic composition in the murine brain.","authors":"Esther Lahoud, Frédéric Moynier, Tu-Han Luu, Brandon Mahan, Marie Le Borgne","doi":"10.1093/mtomcs/mfae008","DOIUrl":"10.1093/mtomcs/mfae008","url":null,"abstract":"Aging is the main risk factor for Alzheimer's disease (AD). AD is linked to alterations in metal homeostasis and changes in stable metal isotopic composition can occur, possibly allowing the latter to serve as relevant biomarkers for potential AD diagnosis. Copper stable isotopes are used to investigate changes in Cu homeostasis associated with various diseases. Prior work has shown that in AD mouse models, the accumulation of 63Cu in the brain is associated with the disease's progression. However, our understanding of how the normal aging process influences the brain's isotopic composition of copper remains limited. In order to determine the utility and predictive power of Cu isotopes in AD diagnostics, we aim-in this study-to develop a baseline trajectory of Cu isotopic composition in the normally aging mouse brain. We determined the copper concentration and isotopic composition in brains of 30 healthy mice (WT) ranging in age from 6 to 12 mo, and further incorporate prior data obtained for 3-mo-old healthy mice; this range approximately equates to 20-50 yr in human equivalency. A significant 65Cu enrichment has been observed in the 12-mo-old mice compared to the youngest group, concomitant with an increase in Cu concentration with age. Meanwhile, literature data for brains of AD mice display an enrichment in 63Cu isotope compared to WT. It is acutely important that this baseline enrichment in 65Cu is fully constrained and normalized against if any coherent diagnostic observations regarding 63Cu enrichment as a biomarker for AD are to be developed.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Co-exposure to lead and high-fat diet aggravates systemic inflammation in mice by altering gut microbiota and the LPS/TLR4 pathway. 通过改变肠道微生物群和 LPS/TLR4 通路，共同暴露于铅和高脂饮食会加重小鼠的全身炎症。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae022

Nana Wang, Changhao Li, Xue Gao, Yuan Huo, Yuting Li, Fangru Cheng, Fei Jiang, Zengli Zhang

{"title":"Co-exposure to lead and high-fat diet aggravates systemic inflammation in mice by altering gut microbiota and the LPS/TLR4 pathway.","authors":"Nana Wang, Changhao Li, Xue Gao, Yuan Huo, Yuting Li, Fangru Cheng, Fei Jiang, Zengli Zhang","doi":"10.1093/mtomcs/mfae022","DOIUrl":"10.1093/mtomcs/mfae022","url":null,"abstract":"This study reports the toxicity of Pb exposure on systemic inflammation in high-fat-diet (HFD) mice and the potential mechanisms. Results indicated that Pb exacerbated intestinal barrier damage and increased serum levels of lipopolysaccharide (LPS) and diamine oxidase in HFD mice. Elevated LPS activates the colonic and ileal LPS-TLR4 inflammatory signaling pathway and further induces hepatic and adipose inflammatory expression. The 16S rRNA gene sequencing results showed that Pb promoted the abundance of potentially harmful and LPS-producing bacteria such as Coriobacteriaceae_UCG-002, Alloprevotella, and Oscillibacter in the intestines of HFD mice, and their abundance was positively correlated with LPS levels. Additionally, Pb inhibited the abundance of the beneficial bacteria Akkermansia, resulting in lower levels of the metabolite short-chain fatty acids (SCFAs). Meanwhile, Pb inhibited adenosine 5'-monophosphate-activated protein kinase signaling-mediated lipid metabolism pathways, promoting hepatic lipid accumulation. The above results suggest that Pb exacerbates systemic inflammation and lipid disorders in HFD mice by altering the gut microbiota, intestinal barrier, and the mediation of metabolites LPS and SCFAs. Our study provides potential novel mechanisms of human health related to Pb-induced metabolic damage and offers new evidence for a comprehensive assessment of Pb risk.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846510","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}

引用次数: 0

Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification. 铁硫蛋白奥德赛：探索其集群功能多样性和具有挑战性的鉴定。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae025

Cindy Vallières, Orane Benoit, Olivier Guittet, Meng-Er Huang, Michel Lepoivre, Marie-Pierre Golinelli-Cohen, Laurence Vernis

{"title":"Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification.","authors":"Cindy Vallières, Orane Benoit, Olivier Guittet, Meng-Er Huang, Michel Lepoivre, Marie-Pierre Golinelli-Cohen, Laurence Vernis","doi":"10.1093/mtomcs/mfae025","DOIUrl":"10.1093/mtomcs/mfae025","url":null,"abstract":"Iron-sulfur (Fe-S) clusters are an essential and ubiquitous class of protein-bound prosthetic centers that are involved in a broad range of biological processes (e.g. respiration, photosynthesis, DNA replication and repair and gene regulation) performing a wide range of functions including electron transfer, enzyme catalysis, and sensing. In a general manner, Fe-S clusters can gain or lose electrons through redox reactions, and are highly sensitive to oxidation, notably by small molecules such as oxygen and nitric oxide. The [2Fe-2S] and [4Fe-4S] clusters, the most common Fe-S cofactors, are typically coordinated by four amino acid side chains from the protein, usually cysteine thiolates, but other residues (e.g. histidine, aspartic acid) can also be found. While diversity in cluster coordination ensures the functional variety of the Fe-S clusters, the lack of conserved motifs makes new Fe-S protein identification challenging especially when the Fe-S cluster is also shared between two proteins as observed in several dimeric transcriptional regulators and in the mitoribosome. Thanks to the recent development of in cellulo, in vitro, and in silico approaches, new Fe-S proteins are still regularly identified, highlighting the functional diversity of this class of proteins. In this review, we will present three main functions of the Fe-S clusters and explain the difficulties encountered to identify Fe-S proteins and methods that have been employed to overcome these issues.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper-binding proteins and exonic splicing enhancers and silencers. 铜结合蛋白与外显子剪接增强子和沉默子。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae023

Dara Bakhtiar, Igor Vorechovsky

{"title":"Copper-binding proteins and exonic splicing enhancers and silencers.","authors":"Dara Bakhtiar, Igor Vorechovsky","doi":"10.1093/mtomcs/mfae023","DOIUrl":"10.1093/mtomcs/mfae023","url":null,"abstract":"Eukaryotic DNA codes not only for proteins but contains a wealth of information required for accurate splicing of messenger RNA precursors and inclusion of constitutively or alternatively spliced exons in mature transcripts. This \"auxiliary\" splicing code has been characterized as exonic splicing enhancers and silencers (ESE and ESS). The exact interplay between protein and splicing codes is, however, poorly understood. Here, we show that exons encoding copper-coordinating amino acids in human cuproproteins lack ESEs and/or have an excess of ESSs, yet RNA sequencing and expressed sequence tags data show that they are more efficiently included in mature transcripts by the splicing machinery than average exons. Their largely constitutive inclusion in messenger RNA is facilitated by stronger splice sites, including polypyrimidine tracts, consistent with an important role of the surrounding intron architecture in ensuring high expression of metal-binding residues during evolution. ESE/ESS profiles of codons and entire exons that code for copper-coordinating residues were very similar to those encoding residues that coordinate zinc but markedly different from those that coordinate calcium. Together, these results reveal how the traditional and auxiliary splicing motifs responded to constraints of metal coordination in proteins.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0