Nucleic Acids Research最新文献_第2页

Directed assembly of single-stranded DNA fragments for data storage via protein-free catalytic splint ligation 定向组装单链DNA片段的数据存储通过无蛋白催化夹板连接

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-30 DOI: 10.1093/nar/gkaf582

Gemma Mendonsa, Sriram Chari, Mengdi Bao, Brett Herdendorf, Anil Reddy

引用次数: 0

Rewiring of cell morphology by Small protein B enhances stress tolerance and colonization in Aeromonas veronii under adverse conditions 在逆境条件下，小蛋白B对细胞形态的重塑增强了维氏气单胞菌的抗逆性和定植能力

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-28 DOI: 10.1093/nar/gkaf608

Zucheng Wang, Hanzeng Li, Qi Xu, Xiaoli Jiang, Xiang Ma, Juanjuan Li, Yanqiong Tang, Zhu Liu

{"title":"Rewiring of cell morphology by Small protein B enhances stress tolerance and colonization in Aeromonas veronii under adverse conditions","authors":"Zucheng Wang, Hanzeng Li, Qi Xu, Xiaoli Jiang, Xiang Ma, Juanjuan Li, Yanqiong Tang, Zhu Liu","doi":"10.1093/nar/gkaf608","DOIUrl":"https://doi.org/10.1093/nar/gkaf608","url":null,"abstract":"Pathogens often display morphological plasticity to withstand environmental stress and thrive in complex host immune environments. In this study, we demonstrated the morphological adaptation of Aeromonas veronii, a severe pathogen with a wide environmental distribution. Our results establish the critical role of Small protein B (SmpB) in morphological adaptation and reveal a conserved dual-safety regulatory mechanism mediated by ArgR. A. veronii exhibited morphological changes and gained enhanced stress resistance in response to environmental cues. We identified the trans-translation component SmpB as critical for this morphological adaptation, independent of its canonical role in trans-translation. Furthermore, SmpB transcriptionally up-regulates peptidoglycan biosynthesis genes. A convolutional neural network model predicted ArgR as a transcriptional regulator of smpB. Subsequent biochemical assays confirmed that ArgR directly bound to the smpB promoter and repressed its transcription by sequestering RNA polymerase. Moreover, the interaction between ArgR and SmpB promoted the affinity of ArgR for the smpB promoter. SmpB-mediated morphological rewiring enhanced A. veronii’s intestinal colonization and virulence in a mouse infection model. Collectively, our study reveals a novel mechanism in which SmpB, operating in a negative feedback loop with ArgR, modulates cell wall synthesis and enhances bacterial ecological fitness. These insights into host–pathogen interactions identify promising targets for innovative antimicrobial therapies and diagnostic strategies.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"17 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503632","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

G-quadruplex topologies determine the functional outcome of guanine-rich bioactive oligonucleotides g -四重体拓扑结构决定了富鸟嘌呤生物活性寡核苷酸的功能结局

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-28 DOI: 10.1093/nar/gkaf590

Prakash Kharel, Nupur Bhatter, Safiyah Zubair, Shawn M Lyons, Paul J Anderson, Pavel Ivanov

{"title":"G-quadruplex topologies determine the functional outcome of guanine-rich bioactive oligonucleotides","authors":"Prakash Kharel, Nupur Bhatter, Safiyah Zubair, Shawn M Lyons, Paul J Anderson, Pavel Ivanov","doi":"10.1093/nar/gkaf590","DOIUrl":"https://doi.org/10.1093/nar/gkaf590","url":null,"abstract":"Guanine-rich nucleic acid sequences can exert sequence- and/or structure-specific activities to influence biological and pathobiological cellular processes. As such, it has been reported that different G-rich oligonucleotides (both DNA and RNA) can have cytotoxic as well as cytoprotective effects on the cells. However, the mechanisms of such a biological outcome are unclear. Here, we report that G-rich DNA oligonucleotides (ODNs) that can form four-stranded secondary structures called G-quadruplexes (G4s) have a topology-dependent biological outcome. Using different biochemical, biophysical, and cellular approaches, we demonstrate that only the parallel topology G4-forming ODNs can repress eukaryotic messenger RNA (mRNA) translation by directly interacting with eukaryotic translation initiation protein 1 (EIF4G1), while the anti-parallel topology G4s do not have inhibitory effect on mRNA translation. These results directly connect the G4 topological differences within ODNs to differential functional impacts in mRNA translation intrans. Our study provides the foundation for the rational design of G-rich oligonucleotides for a desired therapeutic outcome.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"54 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503631","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

The 23rd annual Nucleic Acids Research Web Server Issue 2025. 第二十三届年度核酸研究网络服务器问题2025。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-28 DOI: 10.1093/nar/gkaf564

引用次数: 0

Analysis of natural structures and chemical mapping data reveals local stability compensation in RNA 自然结构分析和化学作图数据揭示了RNA的局部稳定性补偿

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-26 DOI: 10.1093/nar/gkaf565

Robert L Cornwell-Arquitt, Riley Nigh, Michael T Hathaway, Joseph D Yesselman, David A Hendrix

{"title":"Analysis of natural structures and chemical mapping data reveals local stability compensation in RNA","authors":"Robert L Cornwell-Arquitt, Riley Nigh, Michael T Hathaway, Joseph D Yesselman, David A Hendrix","doi":"10.1093/nar/gkaf565","DOIUrl":"https://doi.org/10.1093/nar/gkaf565","url":null,"abstract":"RNA molecules adopt complex structures that perform essential biological functions across all forms of life, making them promising candidates for therapeutic applications. However, our ability to design new RNA structures remains limited by an incomplete understanding of their folding principles. While global metrics such as the minimum free energy are widely used, they are at odds with naturally occurring structures and incompatible with established design rules. Here, we introduce local stability compensation (LSC), a principle that RNA folding is governed by the local balance between destabilizing loops and their stabilizing adjacent stems, challenging the focus on global energetic optimization. Analysis of over 100 000 RNA structures revealed that LSC signatures are particularly pronounced in bulges and their adjacent stems, with distinct patterns across different RNA families that align with their biological functions. To validate LSC experimentally, we systematically analyzed thousands of RNA variants using DMS chemical mapping. Our results demonstrate that stem folding, as measured by reactivity, correlates with LSC (R² = 0.458 for hairpin loops) and that instabilities show no significant effect on folding for distal stems. These findings demonstrate that LSC can be a guiding principle for understanding RNA function and for the rational design of custom RNAs.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"22 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488729","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

Identification of a minimal Alu domain required for retrotransposition 反转位所需的最小Alu域的识别

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-26 DOI: 10.1093/nar/gkaf526

John B Moldovan, John Yin, John V Moran

{"title":"Identification of a minimal Alu domain required for retrotransposition","authors":"John B Moldovan, John Yin, John V Moran","doi":"10.1093/nar/gkaf526","DOIUrl":"https://doi.org/10.1093/nar/gkaf526","url":null,"abstract":"Alu elements are primate-specific retrotransposons that comprise ∼11% of human DNA. Alu sequences contain an internal RNA polymerase III promoter, and the resultant Alu RNA transcripts mobilize by a replicative process termed retrotransposition, which requires the long interspersed element-1 open reading frame 2-encoded protein (ORF2p). Here, we used HeLa cell-based retrotransposition assays to define a minimal Alu domain necessary for retrotransposition. We demonstrate that Alu transcripts expressed from a cytomegalovirus (CMV) RNA polymerase II promoter can efficiently undergo retrotransposition. The use of an external CMV promoter to express Alu RNA allowed us to construct separation-of-function mutations to examine the effects of large deletions within the Alu sequence on retrotransposition. Deletion mutagenesis demonstrated that a 46-nucleotide (nt) domain located at the 5′ end of the Alu RNA transcript is necessary for retrotransposition. Consistent with current models, the 46-nt 5′ Alu domain associates with SRP9/14 in HeLa-HA cell extracts and can promote retrotransposition in HeLa-HA cells. We propose that the 46-nt 5′ Alu domain forms a discrete structure that allows for SRP9/14 binding and ribosomal association, thereby allowing the Alu poly(A) tract to compete with the L1 poly(A) tail for ORF2p RNA binding to mediate its retrotransposition.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"90 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488727","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

Mutational analysis of the F plasmid partitioning protein ParA reveals residues required for oligomerization and plasmid maintenance F质粒分配蛋白ParA的突变分析揭示了寡聚化和质粒维持所需的残基

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-25 DOI: 10.1093/nar/gkaf537

Nivedita Mitra, Dipika Mishra, Manasi Mudaliyar, Rinku Yadav, Suyog Zinjurte, Irene Aniyan Puthethu, Pananghat Gayathri, Debnath Ghosal, Ramanujam Srinivasan

{"title":"Mutational analysis of the F plasmid partitioning protein ParA reveals residues required for oligomerization and plasmid maintenance","authors":"Nivedita Mitra, Dipika Mishra, Manasi Mudaliyar, Rinku Yadav, Suyog Zinjurte, Irene Aniyan Puthethu, Pananghat Gayathri, Debnath Ghosal, Ramanujam Srinivasan","doi":"10.1093/nar/gkaf537","DOIUrl":"https://doi.org/10.1093/nar/gkaf537","url":null,"abstract":"Mobile genetic elements such as plasmids play a crucial role in the emergence of antimicrobial resistance. Hence, plasmid maintenance proteins such as ParA of the Walker A-type ATPases/ParA superfamily are potential targets for novel antibiotics. Plasmid partitioning by ParA relies on ATP-dependent dimerization and formation of chemophoretic gradients of ParA-ATP on bacterial nucleoids. Though polymerization of ParA has been reported in many instances, the need for polymerization in plasmid maintenance remains unclear. In this study, we provide insights into the polymerization of ParA and the effect of polymerization on plasmid maintenance. We report two mutations, Q351H and W362E, in ParA from the F plasmid (ParAF) that form cytoplasmic filaments independent of the ParBSF partitioning complex. Both variants fail to partition plasmids, do not bind non-specific DNA, and act as super-repressors to suppress transcription from the ParAF promoter. Further, we show that the polymerization of ParAF requires an ATP-dependent conformational switch. We identify two residues, R320 in helix 12 and E375 in helix 14 at the interface of the predicted ParAF filament structure, whose mutations abolish filament assembly of ParAF W362E and affect plasmid partitioning. Our results thus suggest a role for the C-terminal helix of ParAF in plasmid maintenance and assembly into higher order structures.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"67 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488728","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

Oxidative stress elicited by phage infection induces Staphylococcal type III-A CRISPR-Cas system. 噬菌体感染引起的氧化应激诱导葡萄球菌III-A型CRISPR-Cas系统。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-20 DOI: 10.1093/nar/gkaf541

Yang Li,Changbin Zhao,Yingqian Cao,Xinhai Chen,Yuanyue Tang,Xiaohui Zhou,Hanne Ingmer,Xinan Jiao,Qiuchun Li

{"title":"Oxidative stress elicited by phage infection induces Staphylococcal type III-A CRISPR-Cas system.","authors":"Yang Li,Changbin Zhao,Yingqian Cao,Xinhai Chen,Yuanyue Tang,Xiaohui Zhou,Hanne Ingmer,Xinan Jiao,Qiuchun Li","doi":"10.1093/nar/gkaf541","DOIUrl":"https://doi.org/10.1093/nar/gkaf541","url":null,"abstract":"In prokaryotes, the CRISPR-Cas system provides immunity to invading mobile genetic elements, but its expression is commonly repressed in the absence of phage infection to prevent autoimmunity. How bacteria senses phage infection and activates CRISPR-Cas system are poorly understood. Here, we demonstrate that an essential promoter Pcas, located within the cas1 gene, is the primary promoter driving expression of cas genes encoding the Cas10-Csm interference complex in Staphylococcus aureus type III-A CRISPR-Cas system during phage infection. As a conserved promoter in Staphylococci type III-A CRISPR-Cas system, the Pcas loses its ability to activate cas genes expression when mutated at the C186 site. Importantly, we find that the transcriptional regulator MgrA directly represses type III-A CRISPR-Cas system by interacting with Pcas to prevent autoimmunity. Upon phage infection, MgrA senses oxidative stress and dissociates from the Pcas, alleviating the transcriptional repression and subsequently triggering a robust immunity against phages. Our work provides evidence for the requirement of Pcas within cas1 during type III-A CRISPR-Cas interference stage, and reveals that MgrA-mediated regulation provides an effective mechanism for bacteria to balance avoiding autoimmunityand defending against phages.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"48 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370334","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

Correction to 'Delineation of pentatricopeptide repeat codes for target RNA prediction'. 更正了“描述用于靶RNA预测的五肽重复代码”。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-20 DOI: 10.1093/nar/gkaf605

引用次数: 0

A solid-phase enzymatic synthesis platform for the facile production of 2'-fluoroarabinonucleic acid (FANA) and chimeric XNA oligonucleotides using an evolved XNA polymerase. 一个固相酶合成平台，用于使用进化的XNA聚合酶，方便地生产2'-氟阿拉伯核酸（FANA）和嵌合XNA寡核苷酸。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-06-20 DOI: 10.1093/nar/gkaf567

Binliang Zhang,Yuhui Du,Jingxing Zhang,Xingyun Ma,Yanjia Qin,Rui Tao,Minglan Luo,Jing Wu,Leping Sun,Gan Zhu,Hantao Luo,Junlin Wen,Chenghe Xiong,Hui Mei,Tingjian Chen

{"title":"A solid-phase enzymatic synthesis platform for the facile production of 2'-fluoroarabinonucleic acid (FANA) and chimeric XNA oligonucleotides using an evolved XNA polymerase.","authors":"Binliang Zhang,Yuhui Du,Jingxing Zhang,Xingyun Ma,Yanjia Qin,Rui Tao,Minglan Luo,Jing Wu,Leping Sun,Gan Zhu,Hantao Luo,Junlin Wen,Chenghe Xiong,Hui Mei,Tingjian Chen","doi":"10.1093/nar/gkaf567","DOIUrl":"https://doi.org/10.1093/nar/gkaf567","url":null,"abstract":"Xenobiotic nucleic acids (XNAs) significantly expand the range of genetic polymers and serve as promising alternatives to DNA and RNA for numerous biological applications. However, the extensive exploration and application of XNAs are limited by low sustainability and yields in solid-phase oligonucleotide synthesis, as well as by the unavailability of efficient XNA polymerases for polymerase-mediated XNA production. To address the limitations in XNA production, we developed a solid-phase enzymatic XNA oligonucleotide synthesis platform using a laboratory-evolved XNA polymerase, SFM5-7, which exhibits excellent activity for synthesizing DNA, RNA, 2'-fluoroarabinonucleic acid (FANA), and other 2'-modified XNA oligonucleotides. This platform employs ribonucleotide insertion and alkaline cleavage of the oligonucleotide product before and after SFM5-7-mediated XNA synthesis, enabling recycled XNA synthesis through the reuse of a bead-immobilized self-priming hairpin DNA template. The platform's potential and versatility are demonstrated by the production of FANA, 2'-modified RNAs, chimeric XNAs, 5'-end-labeled FANA, and an active FANAzyme. This platform should facilitate the customized production of functional XNAs with programmable modifications, accelerating their applications in biotechnology and biomedicine.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"17 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488174","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