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Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens 代谢拔河:微生物代谢形成对肠道病原体的定植抗性
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.005
Katerina Jones , Camila Bernardo de Brito , Mariana Xavier Byndloss
{"title":"Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens","authors":"Katerina Jones ,&nbsp;Camila Bernardo de Brito ,&nbsp;Mariana Xavier Byndloss","doi":"10.1016/j.chembiol.2024.12.005","DOIUrl":"10.1016/j.chembiol.2024.12.005","url":null,"abstract":"<div><div>A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential. This review will focus on recent studies of metabolism-mediated mechanisms of colonization resistance and virulence strategies enteric pathogens use to overcome them, along with how induction of inflammation by pathogenic bacteria changes the landscape of the gut and enables alternative metabolic pathways. We will focus on how intestinal pathogens counteract the protective effects of microbiota-derived metabolites to illustrate the growing appreciation of how metabolic factors may serve as crucial virulence determinants and overcome colonization resistance.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 46-60"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration 微生物衍生代谢物对神经退行性病变产生影响的机制
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.08.014
Lara Kern , Ignacio Mastandrea , Anna Melekhova , Eran Elinav
{"title":"Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration","authors":"Lara Kern ,&nbsp;Ignacio Mastandrea ,&nbsp;Anna Melekhova ,&nbsp;Eran Elinav","doi":"10.1016/j.chembiol.2024.08.014","DOIUrl":"10.1016/j.chembiol.2024.08.014","url":null,"abstract":"<div><div>Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the ‘sterile’ host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 25-45"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases 肠道微生物相关胆盐水解酶底物特异性的化学蛋白质组学分析
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.05.009
Lin Han , Augustus Pendleton , Adarsh Singh , Raymond Xu , Samantha A. Scott , Jaymee A. Palma , Peter Diebold , Kien P. Malarney , Ilana L. Brito , Pamela V. Chang
{"title":"Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases","authors":"Lin Han ,&nbsp;Augustus Pendleton ,&nbsp;Adarsh Singh ,&nbsp;Raymond Xu ,&nbsp;Samantha A. Scott ,&nbsp;Jaymee A. Palma ,&nbsp;Peter Diebold ,&nbsp;Kien P. Malarney ,&nbsp;Ilana L. Brito ,&nbsp;Pamela V. Chang","doi":"10.1016/j.chembiol.2024.05.009","DOIUrl":"10.1016/j.chembiol.2024.05.009","url":null,"abstract":"<div><div><span><span>The gut microbiome<span> possesses numerous biochemical enzymes<span><span> that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in </span>bile acid metabolism<span><span> is bile salt </span>hydrolase (BSH), which controls the host’s overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the </span></span></span></span>gut microbiota<span>, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various </span></span>inflammatory diseases.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 145-156.e9"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome 评论衍生色氨酸代谢物强化皮肤屏障:来自人类皮肤微生物组的50种非生物模型的见解
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.007
Aayushi Uberoi , Sofía M. Murga-Garrido , Preeti Bhanap , Amy E. Campbell , Simon A.B. Knight , Monica Wei , Anya Chan , Taylor Senay , Saba Tegegne , Ellen K. White , Carrie Hayes Sutter , Clementina Mesaros , Thomas R. Sutter , Elizabeth A. Grice
{"title":"Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome","authors":"Aayushi Uberoi ,&nbsp;Sofía M. Murga-Garrido ,&nbsp;Preeti Bhanap ,&nbsp;Amy E. Campbell ,&nbsp;Simon A.B. Knight ,&nbsp;Monica Wei ,&nbsp;Anya Chan ,&nbsp;Taylor Senay ,&nbsp;Saba Tegegne ,&nbsp;Ellen K. White ,&nbsp;Carrie Hayes Sutter ,&nbsp;Clementina Mesaros ,&nbsp;Thomas R. Sutter ,&nbsp;Elizabeth A. Grice","doi":"10.1016/j.chembiol.2024.12.007","DOIUrl":"10.1016/j.chembiol.2024.12.007","url":null,"abstract":"<div><div>The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood. Tryptophan metabolites are AHR ligands that can be products of microbial metabolism. To identify microbially regulated tryptophan metabolites <em>in vivo</em>, we established a gnotobiotic model colonized with fifty human skin commensals and performed targeted mass spectrometry on murine skin. Indole-related metabolites were enriched in colonized skin compared to germ-free skin. In reconstructed human epidermis and in murine models of atopic-like barrier damage, these metabolites improved barrier repair and function individually and as a cocktail. These results provide a framework for the identification of microbial metabolites that mediate specific host functions, which can guide the development of microbe-based therapies for skin disorders.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 111-125.e6"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Yeast paves the way for cancer immunotherapy 酵母为癌症免疫治疗铺平了道路
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.011
Dingjiacheng Jia , Shujie Chen
{"title":"Yeast paves the way for cancer immunotherapy","authors":"Dingjiacheng Jia ,&nbsp;Shujie Chen","doi":"10.1016/j.chembiol.2024.12.011","DOIUrl":"10.1016/j.chembiol.2024.12.011","url":null,"abstract":"<div><div>In this issue of <em>Cell Chemical Biology</em>, Rebeck et al.<span><span><sup>1</sup></span></span> construct a system that enables <em>Saccharomyces cerevisiae</em> var. <em>boulardii</em> (<em>Sb</em>) to secrete immune checkpoint inhibitors, reducing intestinal tumor load. This safe and effective delivery platform using engineered yeast demonstrates potential for enhancing the efficacy of biologics.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 9-11"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches 钙调磷酸酶:通过生物化学、生物化学和遗传方法揭示睡眠的重要调节因子
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.003
Jianjun Yu (余建军) , Huijie Liu (刘慧洁) , Rui Gao (高瑞) , Tao V. Wang (王涛) , Chenggang Li (李成钢) , Yuxiang Liu (刘玉祥) , Lu Yang (杨璐) , Ying Xu (徐颖) , Yunfeng Cui (崔云凤) , Chenxi Jia (贾辰熙) , Juan Huang (黄娟) , Peng R. Chen (陈鹏) , Yi Rao (饶毅)
{"title":"Calcineurin: An essential regulator of sleep revealed by biochemical, chemical biological, and genetic approaches","authors":"Jianjun Yu (余建军) ,&nbsp;Huijie Liu (刘慧洁) ,&nbsp;Rui Gao (高瑞) ,&nbsp;Tao V. Wang (王涛) ,&nbsp;Chenggang Li (李成钢) ,&nbsp;Yuxiang Liu (刘玉祥) ,&nbsp;Lu Yang (杨璐) ,&nbsp;Ying Xu (徐颖) ,&nbsp;Yunfeng Cui (崔云凤) ,&nbsp;Chenxi Jia (贾辰熙) ,&nbsp;Juan Huang (黄娟) ,&nbsp;Peng R. Chen (陈鹏) ,&nbsp;Yi Rao (饶毅)","doi":"10.1016/j.chembiol.2024.12.003","DOIUrl":"10.1016/j.chembiol.2024.12.003","url":null,"abstract":"<div><div>Research into mechanisms underlying sleep traditionally relies on electrophysiology and genetics. Because sleep can only be measured on whole animals by behavioral observations and physical means, no sleep research was initiated by biochemical and chemical biological approaches. We used phosphorylation sites of kinases important for sleep as targets for biochemical and chemical biological approaches. Sleep was increased in mice carrying a threonine-to-alanine substitution at residue T469 of salt-inducible kinase 3 (SIK3). Our biochemical purification and photo-crosslinking revealed calcineurin (CaN) dephosphorylation, both <em>in vitro</em> and <em>in vivo</em>, of SIK3 at T469 and S551, but not T221. Knocking down CaN regulatory subunit reduced daily sleep by more than 5 h, exceeding all known mouse mutants. Our work uncovered a critical physiological role for CaN in sleep and pioneered biochemical purification and chemical biology as effective approaches to study sleep.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 157-173.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology 肠道微生物群与表观遗传学之间的化学相互作用:对昼夜节律生物学的影响
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.04.016
Samskrathi Aravinda Sharma , Sarah Olanrewaju Oladejo , Zheng Kuang
{"title":"Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology","authors":"Samskrathi Aravinda Sharma ,&nbsp;Sarah Olanrewaju Oladejo ,&nbsp;Zheng Kuang","doi":"10.1016/j.chembiol.2024.04.016","DOIUrl":"10.1016/j.chembiol.2024.04.016","url":null,"abstract":"<div><div>Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 61-82"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Meet the authors: Aayushi Uberoi and Elizabeth A. Grice 来认识一下这篇文章的作者:银井青史和伊丽莎白·a·格赖斯
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.010
Aayushi Uberoi, Elizabeth A. Grice
{"title":"Meet the authors: Aayushi Uberoi and Elizabeth A. Grice","authors":"Aayushi Uberoi,&nbsp;Elizabeth A. Grice","doi":"10.1016/j.chembiol.2024.12.010","DOIUrl":"10.1016/j.chembiol.2024.12.010","url":null,"abstract":"<div><div>In an interview with Samantha Nelson, a scientific editor of <em>Cell Chemical Biology</em>, the authors of the research article entitled “Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome” share insights about their paper, field, and lives as scientists.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 1-2"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain β-羟基丁酸盐是老年人和阿尔茨海默病患者大脑中蛋白质平衡的代谢调节剂
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.11.001
Sidharth S. Madhavan , Stephanie Roa Diaz , Sawyer Peralta , Mitsunori Nomura , Christina D. King , Kaya E. Ceyhan , Anwen Lin , Dipa Bhaumik , Anna C. Foulger , Samah Shah , Thanh Blade , Wyatt Gray , Manish Chamoli , Brenda Eap , Oishika Panda , Diego Diaz , Thelma Y. Garcia , Brianna J. Stubbs , Scott M. Ulrich , Gordon J. Lithgow , John C. Newman
{"title":"β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain","authors":"Sidharth S. Madhavan ,&nbsp;Stephanie Roa Diaz ,&nbsp;Sawyer Peralta ,&nbsp;Mitsunori Nomura ,&nbsp;Christina D. King ,&nbsp;Kaya E. Ceyhan ,&nbsp;Anwen Lin ,&nbsp;Dipa Bhaumik ,&nbsp;Anna C. Foulger ,&nbsp;Samah Shah ,&nbsp;Thanh Blade ,&nbsp;Wyatt Gray ,&nbsp;Manish Chamoli ,&nbsp;Brenda Eap ,&nbsp;Oishika Panda ,&nbsp;Diego Diaz ,&nbsp;Thelma Y. Garcia ,&nbsp;Brianna J. Stubbs ,&nbsp;Scott M. Ulrich ,&nbsp;Gordon J. Lithgow ,&nbsp;John C. Newman","doi":"10.1016/j.chembiol.2024.11.001","DOIUrl":"10.1016/j.chembiol.2024.11.001","url":null,"abstract":"<div><div>Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain <em>in vivo</em> after delivery of a ketone ester. This mechanism is selective for pathological proteins such as amyloid-β, and exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We generate libraries of the βHB-induced protein insolublome using mass spectrometry proteomics, and identify common protein domains and upstream regulators. We show enrichment of neurodegeneration-related proteins among βHB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 1","pages":"Pages 174-191.e8"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
RNA infrastructure profiling illuminates transcriptome structure in crowded spaces RNA 基础结构剖析揭示拥挤空间中的转录组结构
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-12-19 DOI: 10.1016/j.chembiol.2024.09.009
Lu Xiao , Linglan Fang , Wenrui Zhong , Eric T. Kool
{"title":"RNA infrastructure profiling illuminates transcriptome structure in crowded spaces","authors":"Lu Xiao ,&nbsp;Linglan Fang ,&nbsp;Wenrui Zhong ,&nbsp;Eric T. Kool","doi":"10.1016/j.chembiol.2024.09.009","DOIUrl":"10.1016/j.chembiol.2024.09.009","url":null,"abstract":"<div><div>RNAs fold into compact structures and undergo protein interactions in cells. These occluded environments can block reagents that probe the underlying RNAs. Probes that can analyze structure in crowded settings can shed light on RNA biology. Here, we employ 2′-OH-reactive probes that are small enough to access folded RNA structure underlying close molecular contacts within cells, providing considerably broader coverage for intracellular RNA structural analysis. The data are analyzed first with well-characterized human ribosomal RNAs and then applied transcriptome-wide to polyadenylated transcripts. The smallest probe acetylimidazole (AcIm) yields 80% greater structural coverage than larger conventional reagent NAIN3, providing enhanced structural information in hundreds of transcripts. The acetyl probe also provides superior signals for identifying m<sup>6</sup>A modification sites in transcripts, particularly in sites that are inaccessible to a standard probe. Our strategy enables profiling RNA infrastructure, enhancing analysis of transcriptome structure, modification, and intracellular interactions, especially in spatially crowded settings.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 12","pages":"Pages 2156-2167.e5"},"PeriodicalIF":6.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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