Nucleic Acids Research最新文献_第10页

Next generation genetic screens in kinetoplastids. 着丝质体的下一代遗传筛选。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf515

James Budzak, T Nicolai Siegel

{"title":"Next generation genetic screens in kinetoplastids.","authors":"James Budzak, T Nicolai Siegel","doi":"10.1093/nar/gkaf515","DOIUrl":"10.1093/nar/gkaf515","url":null,"abstract":"The genomes of all organisms encode diverse functional elements, including thousands of genes and essential noncoding regions for gene regulation and genome organization. Systematic perturbation of these elements is crucial to understanding their roles and how their disruption impacts cellular function. Genetic perturbation approaches, which disrupt gene expression or function, provide valuable insights by linking genetic changes to observable phenotypes. However, perturbing individual genomic elements one at a time is impractical. Genetic screens overcome this limitation by enabling the simultaneous perturbation of numerous genomic elements within a single experiment. Traditionally, these screens relied on simple, high-throughput readouts such as cell fitness, differentiation, or one-dimensional fluorescence. However, recent advancements have introduced powerful technologies that combine genetic screens with image-based and single-cell sequencing readouts, allowing researchers to study how perturbations affect complex cellular phenotypes on a genome-wide scale. These innovations, alongside the development of CRISPR-Cas technologies, have significantly enhanced the precision, efficiency, and scalability of genetic screening approaches. In this review, we discuss the genetic screens performed in kinetoplastid parasites to date, emphasizing their application to both coding and noncoding regions of the genome. Furthermore, we explore how integrating image-based and single-cell sequencing technologies with genetic screens holds the potential to deliver unprecedented insights into cellular function and regulatory mechanisms.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

p53 reveals principles of chromatin remodeling and enhancer activation P53揭示了染色质重塑和增强子激活的原理

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf465

Martin Fischer, Robert Schwarz, Konstantin Riege, Silke Förste, Katjana Schwab, Elina Wiechens, Alena van Bömmel, Steve Hoffmann

{"title":"p53 reveals principles of chromatin remodeling and enhancer activation","authors":"Martin Fischer, Robert Schwarz, Konstantin Riege, Silke Förste, Katjana Schwab, Elina Wiechens, Alena van Bömmel, Steve Hoffmann","doi":"10.1093/nar/gkaf465","DOIUrl":"https://doi.org/10.1093/nar/gkaf465","url":null,"abstract":"Pioneer transcription factors can bind to closed chromatin, initiating its opening and subsequent gene activation. However, the specific features that enable transcription factors to activate particular loci remain largely undefined. Here, we show that the transcription factor p53 unexpectedly initiates epigenetic remodeling at the majority of its binding sites and drives transcription at select loci. Our quantitative epigenetic data reveal that p53 establishes new enhancers, while quantitative transcription initiation analyses indicate that high local p53 abundance and sequence-specific binding are key features of sites where p53 successfully induces transcription. Surprisingly, we observed a spatial overlap between p53 binding sites and transcription initiation sites, suggesting a decoupling of these two events. Our results reveal that p53 activity unfolds across three distinct layers: histone modification, nucleosome eviction, and transcription initiation, with the latter driven by dynamic rather than static p53 DNA binding. These insights expand our understanding of the function of p53 by showing it not only actively initiates transcription but also broadly remodels chromatin. Overall, these findings offer a conceptual framework to explore how transcription factors regulate chromatin states and gene expression.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"16 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis. 在有丝分裂中，KIF2C缩合将PLK1和磷酸化的BRCA2集中在着丝点微管上。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf476

Anastasiia Skobelkina, Manon Julien, Sylvain Jeannin, Simona Miron, Tom Egger, Rady Chaaban, Guillaume Bouvignies, Emile Alghoul, Rania Ghouil, Claire Friel, Didier Busso, Juan C Cañas, François-Xavier Theillet, Romain Le Bars, Aura Carreira, Angelos Constantinou, Jihane Basbous, Sophie Zinn-Justin

{"title":"KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis.","authors":"Anastasiia Skobelkina, Manon Julien, Sylvain Jeannin, Simona Miron, Tom Egger, Rady Chaaban, Guillaume Bouvignies, Emile Alghoul, Rania Ghouil, Claire Friel, Didier Busso, Juan C Cañas, François-Xavier Theillet, Romain Le Bars, Aura Carreira, Angelos Constantinou, Jihane Basbous, Sophie Zinn-Justin","doi":"10.1093/nar/gkaf476","DOIUrl":"10.1093/nar/gkaf476","url":null,"abstract":"During mitosis, the microtubule depolymerase KIF2C, the tumor suppressor BRCA2, and the kinase PLK1 contribute to the control of kinetochore-microtubule attachments. Both KIF2C and BRCA2 are phosphorylated by PLK1, and BRCA2 phosphorylated at T207 (BRCA2-pT207) serves as a docking site for PLK1. Reducing this interaction results in unstable microtubule-kinetochore attachments. Here we identified that KIF2C also directly interacts with BRCA2-pT207. Indeed, the N-terminal domain of KIF2C adopts a Tudor/PWWP/MBT fold that unexpectedly binds to phosphorylated motifs. Using an optogenetic platform, we found that KIF2C forms membrane-less organelles that assemble through interactions mediated by this phospho-binding domain. KIF2C condensation does not depend on BRCA2-pT207 but requires active Aurora B and PLK1 kinases. Moreover, it concentrates PLK1 and BRCA2-pT207 in an Aurora B-dependent manner. Finally, KIF2C depolymerase activity promotes the formation of KIF2C condensates, but strikingly, KIF2C condensates exclude tubulin: they are located on microtubules, especially at their extremities. Altogether, our results suggest that, during the attachment of kinetochores to microtubules, the assembly of KIF2C condensates amplifies PLK1 and KIF2C catalytic activities and spatially concentrates BRCA2-pT207 at the extremities of microtubules. We propose that this novel and highly regulated mechanism contributes to the control of microtubule-kinetochore attachments, chromosome alignment, and stability.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The functionality of telomerase depends on CPF-CF induced 3'end processing of its RNA component TLC1 and a novel Nrd1-Nab3 surveillance mechanism. 端粒酶的功能依赖于CPF-CF诱导其RNA组分TLC1的3'端加工和一种新的Nrd1-Nab3监视机制。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf480

Jan-Philipp Lamping, Heike Krebber

{"title":"The functionality of telomerase depends on CPF-CF induced 3'end processing of its RNA component TLC1 and a novel Nrd1-Nab3 surveillance mechanism.","authors":"Jan-Philipp Lamping, Heike Krebber","doi":"10.1093/nar/gkaf480","DOIUrl":"10.1093/nar/gkaf480","url":null,"abstract":"Telomere elongation is driven by telomerase, which consists of several proteins and the ncRNA component TLC1 in yeast. While many ncRNAs are terminated via the Nrd1-Nab3-Sen1 (NNS) pathway, we found that TLC1 requires cleavage and polyadenylation factor (CPF)-cleavage factor (CF) mediated 3'end processing and the resulting poly(A) tail to mature into a functional ribozyme. The poly(A) tail is predicted to fold back onto (U)-repeats potentially forming a terminal stem-loop structure that supports Sm-ring binding and thereby re-import into the nucleus after cytoplasmic shuttling. However, longer pre-TLC1 transcripts are predicted to fold differently, resulting in Sm-ring and import receptor binding defects, leaving them unable to overcome this cytoplasmic quality control checkpoint. To prevent cytoplasmic leakage of overlong transcripts, we propose an additional nuclear monitoring system, requiring Nrd1-Nab3 binding sites located between the first PAS motifs. CPF-CF formation might compete with Nrd1-Nab3 releasing them from shorter but not from longer transcripts facilitating their decay. This potential competitive RNA-binding of CPF-CF and Nrd1-Nab3 balances stability and decay.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The intrinsic preference of guanosine bases for cleavage-facilitating interactions with phosphodiester moieties in RNA anions revealed by base modifications and mass spectrometry. 通过碱基修饰和质谱分析揭示了鸟嘌呤碱基与RNA阴离子中磷酸二酯基团相互作用的内在偏好。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf494

Anna Ploner,Christoph Mitteregger,Heidelinde Glasner,Raphael Bereiter,Ronald Micura,Kathrin Breuker

引用次数: 0

Bright and pH-sensitive Baby Spinach aptamer with RNA triplex fusion. 明亮和ph敏感的婴儿菠菜适体与RNA三重融合。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf151

Kinuko Ueno, Kaori Tsukakoshi, Norito Takeuchi, Shintaro Inaba, Andrea Idili, Alessandro Porchetta, Francesco Ricci, Kazunori Ikebukuro

{"title":"Bright and pH-sensitive Baby Spinach aptamer with RNA triplex fusion.","authors":"Kinuko Ueno, Kaori Tsukakoshi, Norito Takeuchi, Shintaro Inaba, Andrea Idili, Alessandro Porchetta, Francesco Ricci, Kazunori Ikebukuro","doi":"10.1093/nar/gkaf151","DOIUrl":"10.1093/nar/gkaf151","url":null,"abstract":"Herein, we developed a fluorescent RNA aptamer as a pH-sensitive probe for monitoring the intercellular pH condition. We demonstrated that the designed RNA triplex structure can undergo pH-sensitive structural changes and function as a pH-nanoswitch. We then combined a previously reported fluorescent aptamer with an RNA pH-nanoswitch to facilitate it becoming pH-sensitive. Using the triplex-fused fluorescent aptamer, named Bright Baby Spinach aptamer, we successfully demonstrated that this pH probe can quickly and sensitively respond to intercellular changes in pH. Surprisingly, we found that Bright Baby Spinach aptamer showed a strong fluorescence up to 13-fold higher than that of the original aptamer in cells. A possible reason for this enhancement was that the RNA triplex structure may contribute to the appropriate folding of the aptamer to bind and stack with the fluorescent ligand 3,5-difluoro-4-hydroxybenzylidene imidazolinone. Thus, fluorescence-enhanced pH-sensitive Bright Baby Spinach aptamer has the potential for rapidly and sensitively responding to intracellular changes in pH.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137. HIV Vpr激活核仁特异性ATR通路降解核仁应激传感器CCDC137。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf531

Karly A Nisson, Rishi S Patel, Yennifer Delgado, Mehdi Bouhaddou, Lucie Etienne, Oliver I Fregoso

{"title":"HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137.","authors":"Karly A Nisson, Rishi S Patel, Yennifer Delgado, Mehdi Bouhaddou, Lucie Etienne, Oliver I Fregoso","doi":"10.1093/nar/gkaf531","DOIUrl":"10.1093/nar/gkaf531","url":null,"abstract":"The lentiviral accessory protein Vpr engages an extensive network of cellular pathways to drive diverse host consequences. Of its many phenotypes, CRL4A-E3 ubiquitin ligase complex co-option, DNA damage response (DDR) engagement, and G2/M arrest are conserved and thus proposed to be functionally important. How Vpr effects these functions and whether they explain how Vpr dysregulates additional cellular pathways remain unclear. Here we leverage the ability of Vpr to deplete the nucleolar protein CCDC137 to understand how Vpr-induced DDR activation impacts nucleolar processes. We characterize CCDC137 as an indirect Vpr target whose degradation does not correlate with Vpr-induced G2/M arrest. Yet, degradation is conserved among Vpr from the pandemic HIV-1 and related SIVcpz/SIVgor, and it is triggered by genomic insults that activate a nucleolar ATR pathway in a manner similar to camptothecin. We determine that Vpr causes ATR-dependent features of nucleolar stress that correlate with CCDC137 degradation, including redistribution of nucleolar proteins, altered nucleolar morphology, and repressed ribosome biogenesis. Together, these data distinguish CCDC137 as a non-canonical Vpr target that may serve as a sensor of nucleolar disruption, and in doing so, identify a novel role for Vpr in nucleolar stress.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pioneering new enhancers by GATA3: role of facilitating transcription factors and chromatin remodeling 通过GATA3开拓新的增强子：促进转录因子和染色质重塑的作用

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf473

Krystal A Orlando, Sara A Grimm, Paul A Wade

{"title":"Pioneering new enhancers by GATA3: role of facilitating transcription factors and chromatin remodeling","authors":"Krystal A Orlando, Sara A Grimm, Paul A Wade","doi":"10.1093/nar/gkaf473","DOIUrl":"https://doi.org/10.1093/nar/gkaf473","url":null,"abstract":"Pioneer transcription factors (PTFs) bind to inaccessible chromatin and recruit collaborating transcription factors to promote chromatin accessibility. However, mechanisms driving PTFs to specify collaborating transcription factor recruitment and chromatin remodeling remain unclear. Here, we utilize inducible expression of a PTF, GATA3, in a basal breast cancer cell line (SUM159PT) to mechanistically address the collaborating transcription factor requirements and the local chromatin architecture delineating GATA3-depenent chromatin accessibility and enhancer formation (productive sites) versus GATA3-bound inaccessible chromatin (unproductive sites). Transcription factor footprinting in productive sites illustrated enrichment of GATA3 with AP-1 transcription factor. Together, GATA3 and AP-1 colocalize at primed enhancers with p300 and BRG1 where nucleosome positioning is influenced by GATA3 binding. Although inhibition of AP-1 binding affects a small subset of productive sites, we demonstrate that inhibition of SWI/SNF ATPases results in dramatic loss of GATA3-dependent chromatin accessibility, binding, and alterations in local chromatin architecture. We conclude that GATA3-dependent gains in chromatin accessibility require chromatin remodeling and that accessibility at some loci is facilitated by collaborating transcription factors like AP-1.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"10 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Unraveling the regulatory dynamics of bidirectional promoters for modulating gene co-expression and metabolic flux in Saccharomyces cerevisiae. 揭示双向启动子调控酿酒酵母基因共表达和代谢通量的调控动力学。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf511

Zimo Jin, Yueming Dong, Abdul Muntakim Rafi, Md Mohsin Patwary, Catherine Xu, Morten H Raadam, Carl G de Boer, Codruta Ignea

{"title":"Unraveling the regulatory dynamics of bidirectional promoters for modulating gene co-expression and metabolic flux in Saccharomyces cerevisiae.","authors":"Zimo Jin, Yueming Dong, Abdul Muntakim Rafi, Md Mohsin Patwary, Catherine Xu, Morten H Raadam, Carl G de Boer, Codruta Ignea","doi":"10.1093/nar/gkaf511","DOIUrl":"10.1093/nar/gkaf511","url":null,"abstract":"Bidirectional promoters (BDPs) hold great promise for applications in synthetic biology by enabling co-expression of multiple genes with minimized promoter size. However, the lack of well-characterized BDPs along with an incomplete understanding of their regulatory mechanisms limits broader applications. Here, we conducted genome-wide screening and characterization of 749 BDP candidates containing a single shared nucleosome-depleted region in yeast Saccharomyces cerevisiae. A pronounced asymmetry in BDP strength was observed using both transcriptomic and fluorescence reporter analyses. We demonstrated that these unbalanced BDP strengths could be utilized for fine-tuning metabolic flux in yeast, achieving yields comparable to or exceeding those of commonly used constitutive or inducible promoters for terpenoid production under the examined conditions. Using in silico mutagenesis guided by the DREAM-CNN yeast cis-regulatory AI prediction model, we identified conserved activator-binding hotspots within the central region of 63.8% of identified BDP candidates. Disruption of these hotspots in six selected BDPs significantly reduced promoter strength in both orientations, suggesting that these AI-predicted motifs are indeed critical for the functionality of BDPs. Overall, this study provides a comprehensive framework for BDP identification and engineering, leveraging AI-guided models to advance rational synthetic promoter design, thus paving the way for precise genetic control in synthetic biology.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structurally distinct manganese-sensing riboswitch aptamers regulate different expression platform architectures. 结构上不同的锰感应核开关适体调节不同的表达平台结构。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-06-06 DOI: 10.1093/nar/gkaf477

Christine Stephen, Danea E Palmer, Clarisa Bautista, Tatiana V Mishanina

{"title":"Structurally distinct manganese-sensing riboswitch aptamers regulate different expression platform architectures.","authors":"Christine Stephen, Danea E Palmer, Clarisa Bautista, Tatiana V Mishanina","doi":"10.1093/nar/gkaf477","DOIUrl":"10.1093/nar/gkaf477","url":null,"abstract":"Manganese (Mn)-sensing riboswitches protect bacteria from Mn toxicity by upregulating expression of Mn exporters. The Mn aptamers share key features but diverge in other important elements, including within the metal-binding core. Although X-ray crystal structures of isolated aptamers exist, these structural snapshots lack crucial details about how the aptamer communicates the presence or absence of ligand to the expression platform. In this work, we investigated the Mn-sensing translational riboswitches in Escherichia coli (mntP and alx), which differ in aptamer secondary structure, nucleotide sequence, and pH-dependence of Mn response. We performed co-transcriptional RNA chemical probing, allowing us to visualize RNA folding intermediates that form and resolve en route to the final folded riboswitch. For the first time, we report that sampling of metal ions by the RNA begins before the aptamer synthesis and folding are complete. At a single-nucleotide resolution, we pinpoint the transcription window where \"riboswitching\" occurs in response to Mn binding and uncover key differences in how the alx and mntP riboswitches fold. Finally, we describe riboswitch-specific effects of pH, providing insights into how two members of the same riboswitch family differentially sense two distinct environmental cues: concentration of Mn and pH.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 11","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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