Nature chemical biology最新文献_第4页

Single-step discovery of high-affinity RNA ligands by UltraSelex UltraSelex单步发现高亲和力RNA配体

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-31 DOI: 10.1038/s41589-025-01868-6

Yaqing Zhang, Yuan Jiang, David Kuster, Qiwei Ye, Wenhao Huang, Simon Fürbacher, Jingye Zhang, Pia Doll, Wenjun Lin, Siwei Dong, Hui Wang, Zhipeng Tang, David Ibberson, Klemens Wild, Irmgard Sinning, Anthony A. Hyman, Andres Jäschke

{"title":"Single-step discovery of high-affinity RNA ligands by UltraSelex","authors":"Yaqing Zhang, Yuan Jiang, David Kuster, Qiwei Ye, Wenhao Huang, Simon Fürbacher, Jingye Zhang, Pia Doll, Wenjun Lin, Siwei Dong, Hui Wang, Zhipeng Tang, David Ibberson, Klemens Wild, Irmgard Sinning, Anthony A. Hyman, Andres Jäschke","doi":"10.1038/s41589-025-01868-6","DOIUrl":"https://doi.org/10.1038/s41589-025-01868-6","url":null,"abstract":"Aptamers, nucleic acid ligands targeting specific molecules, have emerged as drug candidates, sensors, imaging tools and nanotechnology building blocks. The predominant method for their discovery, systematic evolution of ligands by exponential enrichment, while successful, is laborious, time-consuming and often results in candidates enriched for unintended criteria. Here we present UltraSelex, a noniterative method that combines biochemical partitioning, high-throughput sequencing and computational signal-to-background rank modeling for discovering RNA aptamers in about 1 day. UltraSelex identified high-affinity RNA aptamers capable of binding a fluorogenic silicon rhodamine dye and two protein targets, the SARS-CoV-2 RNA-dependent RNA polymerase and HIV reverse transcriptase, enabling live-cell RNA imaging and efficient enzyme inhibition, respectively. From the ranked sequences, minimal aptamer motifs could be easily inferred. UltraSelex provides a rapid route to reveal new drug candidates and diagnostic tools.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"1 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736722","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

Author Correction: Imaging the dynamics of messenger RNA with a bright and stable green fluorescent RNA 作者更正：用明亮稳定的绿色荧光RNA成像信使RNA的动态

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-28 DOI: 10.1038/s41589-025-01892-6

Fangting Zuo, Li Jiang, Ni Su, Yaqiang Zhang, Bingkun Bao, Limei Wang, Yajie Shi, Huimin Yang, Xinyi Huang, Ruilong Li, Qingmei Zeng, Zhengda Chen, Qiuning Lin, Yingping Zhuang, Yuzheng Zhao, Xianjun Chen, Linyong Zhu, Yi Yang

引用次数: 0

Post-transcriptional modular synthetic receptors 转录后模块合成受体

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-28 DOI: 10.1038/s41589-025-01872-w

Xiaowei Zhang, Luis S. Mille-Fragoso, K. Eerik Kaseniit, Arden P. Lee, Meng Zhang, Connor C. Call, Yixin Hu, Yunxin Xie, Xiaojing J. Gao

引用次数: 0

Trans-splicing for gene regulation 基因调控的反式剪接

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-27 DOI: 10.1038/s41589-025-01871-x

Samat Bayakhmetov, Mahan Naseri, Xiao Wang

引用次数: 0

Reversible histone deacetylase activity catalyzes lysine acylation 可逆组蛋白去乙酰化酶活性催化赖氨酸酰化

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-26 DOI: 10.1038/s41589-025-01869-5

Takeshi Tsusaka, Mohd. Altaf Najar, Benjamin Schwarz, Eric Bohrnsen, Juan A. Oses-Prieto, Helena Neudorf, Christina Lee, Jonathan P. Little, Alma L. Burlingame, Catharine M. Bosio, George M. Burslem, Emily L. Goldberg

{"title":"Reversible histone deacetylase activity catalyzes lysine acylation","authors":"Takeshi Tsusaka, Mohd. Altaf Najar, Benjamin Schwarz, Eric Bohrnsen, Juan A. Oses-Prieto, Helena Neudorf, Christina Lee, Jonathan P. Little, Alma L. Burlingame, Catharine M. Bosio, George M. Burslem, Emily L. Goldberg","doi":"10.1038/s41589-025-01869-5","DOIUrl":"https://doi.org/10.1038/s41589-025-01869-5","url":null,"abstract":"The dynamic modification of proteins by many metabolites suggests an intimate link between energy metabolism and post-translational modifications (PTMs). For instance, starvation and low-carbohydrate diets lead to the accumulation of β-hydroxybutyrate (BHB), whose blood concentrations can reach millimolar levels, concomitant with the accumulation of lysine β-hydroxybutyrylation (Kbhb) of proteins. Here we report that class I histone deacetylases (HDACs) unexpectedly catalyze the formation of Kbhb. Through mutational analysis, we show a shared reliance on key active site amino acids for classical deacetylation and noncanonical HDAC-catalyzed β-hydroxybutyrylation. On the basis of these data, we propose that HDACs catalyze a condensation reaction between the free amine group on lysine and the BHB carboxylic acid, thereby generating an amide bond. This reversible HDAC activity is not limited to BHB and extends to multiple short-chain fatty acids, representing a novel mechanism of PTM deposition relevant to metabolically sensitive proteome modifications.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"71 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702901","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

Pharmacological targeting of BMAL1 modulates circadian and immune pathways BMAL1的药理靶向调节昼夜节律和免疫途径

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-25 DOI: 10.1038/s41589-025-01863-x

Hua Pu, Laura C. Bailey, Ludwig G. Bauer, Maria Voronkov, Matthew Baxter, Kilian V. M. Huber, Sepideh Khorasanizadeh, David Ray, Fraydoon Rastinejad

{"title":"Pharmacological targeting of BMAL1 modulates circadian and immune pathways","authors":"Hua Pu, Laura C. Bailey, Ludwig G. Bauer, Maria Voronkov, Matthew Baxter, Kilian V. M. Huber, Sepideh Khorasanizadeh, David Ray, Fraydoon Rastinejad","doi":"10.1038/s41589-025-01863-x","DOIUrl":"https://doi.org/10.1038/s41589-025-01863-x","url":null,"abstract":"The basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) proteins BMAL1 and CLOCK heterodimerize to form the master transcription factor governing rhythmic gene expression. Owing to connections between circadian regulation and numerous physiological pathways, targeting the BMAL1–CLOCK complex pharmacologically is an attractive entry point for intervening in circadian-related processes. In this study, we developed a small molecule, Core Circadian Modulator (CCM), that targets the cavity in the PASB domain of BMAL1, causing it to expand, leading to conformational changes in the PASB domain and altering the functions of BMAL1 as a transcription factor. Biochemical, structural and cellular investigations validate the high level of selectivity of CCM in engaging BMAL1, enabling direct access to BMAL1–CLOCK cellular activities. CCM induces dose-dependent alterations in PER2–Luc oscillations and orchestrates the downregulation of inflammatory and phagocytic pathways in macrophages. These findings collectively reveal that the BMAL1 protein architecture is inherently configured to enable the binding of chemical ligands for functional modulation.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"97 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695536","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

Learning from CoQ10 history 了解辅酶q10的历史

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-03-24 DOI: 10.1038/s41589-025-01877-5

Francesco Zamberlan

引用次数: 0

Phage-fueled defense system 噬菌体燃料防御系统

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-03-24 DOI: 10.1038/s41589-025-01875-7

Yiyun Song

引用次数: 0

Guiding chemoenzymatic synthesis 指导化学酶合成

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-03-24 DOI: 10.1038/s41589-025-01876-6

Gene Chong

引用次数: 0

CLYBL averts vitamin B12 depletion by repairing malyl-CoA CLYBL通过修复甲基辅酶a来避免维生素B12的消耗

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-19 DOI: 10.1038/s41589-025-01857-9

Corey M. Griffith, Jean-François Conrotte, Parisa Paydar, Xinqiang Xie, Ursula Heins-Marroquin, Floriane Gavotto, Christian Jäger, Kenneth W. Ellens, Carole L. Linster

{"title":"CLYBL averts vitamin B12 depletion by repairing malyl-CoA","authors":"Corey M. Griffith, Jean-François Conrotte, Parisa Paydar, Xinqiang Xie, Ursula Heins-Marroquin, Floriane Gavotto, Christian Jäger, Kenneth W. Ellens, Carole L. Linster","doi":"10.1038/s41589-025-01857-9","DOIUrl":"https://doi.org/10.1038/s41589-025-01857-9","url":null,"abstract":"Citrate lyase beta-like protein (CLYBL) is a ubiquitously expressed mammalian enzyme known for its role in the degradation of itaconate, a bactericidal immunometabolite produced in activated macrophages. The association of CLYBL loss of function with reduced circulating vitamin B12 levels was proposed to result from inhibition of the B12-dependent enzyme methylmalonyl-CoA mutase by itaconyl-CoA. The discrepancy between the highly inducible and locally confined production of itaconate and the broad expression profile of CLYBL across tissues suggested a role for this enzyme beyond itaconate catabolism. Here we discover that CLYBL additionally functions as a metabolite repair enzyme for malyl-CoA, a side product of promiscuous citric acid cycle enzymes. We found that CLYBL knockout cells, accumulating malyl-CoA but not itaconyl-CoA, show decreased levels of adenosylcobalamin and that malyl-CoA is a more potent inhibitor of methylmalonyl-CoA mutase than itaconyl-CoA. Our work thus suggests that malyl-CoA plays a role in the B12 deficiency observed in individuals with CLYBL loss of function.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"25 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654241","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