Nucleic Acids Research最新文献_第5页

Altering translation allows E. coli to overcome G-quadruplex stabilizers

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-08 DOI: 10.1093/nar/gkaf264

Rachel R Cueny, Andrew F Voter, Aidan M McKenzie, Marcel Morgenstern, Kevin S Myers, Michael M Place, Jason M Peters, Joshua J Coon, James L Keck

{"title":"Altering translation allows E. coli to overcome G-quadruplex stabilizers","authors":"Rachel R Cueny, Andrew F Voter, Aidan M McKenzie, Marcel Morgenstern, Kevin S Myers, Michael M Place, Jason M Peters, Joshua J Coon, James L Keck","doi":"10.1093/nar/gkaf264","DOIUrl":"https://doi.org/10.1093/nar/gkaf264","url":null,"abstract":"G-quadruplex (G4) structures can form in guanine-rich DNA or RNA and have been found to modulate cellular processes, including replication, transcription, and translation. Many studies on the cellular roles of G4s have focused on eukaryotic systems, with far fewer probing bacterial G4s. Using a chemical-genetic approach, we identified genes in Escherichia coli that are important for growth in G4-stabilizing conditions. Reducing levels of translation elongation factor Tu or slowing translation initiation or elongation with kasugamycin, chloramphenicol, or spectinomycin suppress the effects of G4-stabilizing compounds. In contrast, reducing the expression of specific translation termination or ribosome recycling proteins is detrimental to growth in G4-stabilizing conditions. Proteomic and transcriptomic analyses reveal decreased protein and transcript levels, respectively, for ribosome assembly factors and proteins associated with translation in the presence of G4 stabilizer. Our results support a model in which reducing the rate of translation by altering translation initiation, translation elongation, or ribosome assembly can compensate for G4-related stress in E. coli.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"24 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797778","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

An enzymatic-independent function of palmitoyl hydrolase in cohesin loading onto chromosome

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-08 DOI: 10.1093/nar/gkaf257

Yi-Ting Wang, Wan-Yi Hsiao, Thanh-Vy Pham, Bo-Ru Huang, Shu-Dan Yeh, En-Chi Hsu, Shao-Win Wang

引用次数: 0

DNA/RNA hybrids avoid channel gating that leads to the continued packaging of numerous hybrids into the phi29 protein shell

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-08 DOI: 10.1093/nar/gkaf242

Dan Shu, Abhjeet S Bhullar, Chenxi Liang, Long Zhang, Peixuan Guo

{"title":"DNA/RNA hybrids avoid channel gating that leads to the continued packaging of numerous hybrids into the phi29 protein shell","authors":"Dan Shu, Abhjeet S Bhullar, Chenxi Liang, Long Zhang, Peixuan Guo","doi":"10.1093/nar/gkaf242","DOIUrl":"https://doi.org/10.1093/nar/gkaf242","url":null,"abstract":"Packaging of double-stranded DNA (dsDNA) into viral capsids is crucial in dsDNA viruses, including herpesviruses, adenoviruses, poxviruses, and bacteriophages. An ATPase motor compacts genomes. The phi29 DNA packaging motor, a model system, employs a hexameric pRNA (packaging RNA) ring and ATPase, sharing a revolving mechanism observed in herpesvirus genome packaging, bacterial DNA transport, Holliday junction resolution, and plasmid conjugation. Channel gating terminates translocation and readies a reversed pore for dsDNA exit; its mechanism is unclear. We report a packaging efficiency difference between dsDNA and RNA/DNA hybrids. Single-channel electrophysiology and sucrose gradient ultracentrifugation reveal that packaging fails if both ends are dsRNA, but succeeds if either 5′ or 3′ end is DNA. As long as one strand is DNA, RNA/DNA hybrids are packaged, with a higher copy number than dsDNA. Single-pore conductance assays show that this efficiency results from the absence of channel gating. The channel remains open during RNA/DNA translocation and does not close after hybrid packaging, implying dsDNA’s role in gating and conformational changes. This gating arises from dsDNA’s interaction with three flexible loops of the motor channel. These findings offer a structural and chemical foundation for designing containers to package RNA/DNA hybrids for gene/RNAi delivery, therapy, synthetic biology, nanotechnology, and single-particle sensing.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"13 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797777","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

Two redox-responsive LysR-type transcription factors control the oxidative stress response of Agrobacterium tumefaciens

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-08 DOI: 10.1093/nar/gkaf267

Janka J Schmidt, Vivian B Brandenburg, Hannah Elders, Saba Shahzad, Sina Schäkermann, Ronja Fiedler, Lisa R Knoke, Yvonne Pfänder, Pascal Dietze, Hannah Bille, Bela Gärtner, Lennart J Albin, Lars I Leichert, Julia E Bandow, Eckhard Hofmann, Franz Narberhaus

{"title":"Two redox-responsive LysR-type transcription factors control the oxidative stress response of Agrobacterium tumefaciens","authors":"Janka J Schmidt, Vivian B Brandenburg, Hannah Elders, Saba Shahzad, Sina Schäkermann, Ronja Fiedler, Lisa R Knoke, Yvonne Pfänder, Pascal Dietze, Hannah Bille, Bela Gärtner, Lennart J Albin, Lars I Leichert, Julia E Bandow, Eckhard Hofmann, Franz Narberhaus","doi":"10.1093/nar/gkaf267","DOIUrl":"https://doi.org/10.1093/nar/gkaf267","url":null,"abstract":"Pathogenic bacteria often encounter fluctuating reactive oxygen species (ROS) levels, particularly during host infection, necessitating robust redox-sensing mechanisms for survival. The LysR-type transcriptional regulator (LTTR) OxyR is a widely conserved bacterial thiol-based redox sensor. However, members of the Rhizobiales also encode LsrB, a second LTTR with potential redox-sensing function. This study explores the roles of OxyR and LsrB in the plant-pathogen Agrobacterium tumefaciens. Through single and combined deletions, we observed increased H2O2 sensitivity, underscoring their function in oxidative defense. Genome-wide transcriptome profiling under H2O2 exposure revealed that OxyR and LsrB co-regulate key antioxidant genes, including katG, encoding a bifunctional catalase/peroxidase. Agrobacterium tumefaciens LsrB possesses four cysteine residues potentially involved in redox sensing. To elucidate the structural basis for redox-sensing, we applied single-particle cryo-EM (cryogenic electron microscopy) to experimentally confirm an AlphaFold model of LsrB, identifying two proximal cysteine pairs. In vitro thiol-trapping coupled with mass spectrometry confirmed reversible thiol modifications of all four residues, suggesting a functional role in redox regulation. Collectively, these findings reveal that A. tumefaciens employs two cysteine-based redox sensing transcription factors, OxyR and LsrB, to withstand oxidative stress encountered in host and soil environments.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"4 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797783","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 differential effect of SARS-CoV-2 NSP1 on mRNA translation and stability reveals new insights linking ribosome recruitment, codon usage, and virus evolution

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-08 DOI: 10.1093/nar/gkaf261

Juan José Berlanga, Tania Matamoros, Miguel Rodríguez Pulido, Margarita Sáiz, Mercedes Núñez Bayón, René Toribio, Iván Ventoso

{"title":"The differential effect of SARS-CoV-2 NSP1 on mRNA translation and stability reveals new insights linking ribosome recruitment, codon usage, and virus evolution","authors":"Juan José Berlanga, Tania Matamoros, Miguel Rodríguez Pulido, Margarita Sáiz, Mercedes Núñez Bayón, René Toribio, Iván Ventoso","doi":"10.1093/nar/gkaf261","DOIUrl":"https://doi.org/10.1093/nar/gkaf261","url":null,"abstract":"The nonstructural protein 1 (NSP1) of SARS-CoV-2 blocks the messenger RNA (mRNA) entry channel of the 40S ribosomal subunit, causing inhibition of translation initiation and subsequent degradation of host mRNAs. However, target mRNA specificity and how viral mRNAs escape NSP1-mediated degradation have not been clarified to date. Here we found that NSP1 acts as a translational switch capable of blocking or enhancing translation depending on how preinitiation complex, 43S-PIC, is recruited to the mRNA, whereas NSP1-mediated mRNA degradation mostly depends on codon usage bias. Thus, fast-translating mRNAs with optimal codon usage for human cells that preferentially recruit 43S-PIC by threading showed a dramatic sensitivity to NSP1. Translation of SARS-CoV-2 mRNAs escapes NSP1-mediated inhibition by a proper combination of suboptimal codon usage and slotting-prone 5′ UTR. Thus, the prevalence of nonoptimal codons found in SARS-CoV-2 and other coronavirus genomes is favored by the distinctive effect that NSP1 plays on translation and mRNA stability.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"26 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797782","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

CellPie: a scalable spatial transcriptomics factor discovery method via joint non-negative matrix factorization

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-01 DOI: 10.1093/nar/gkaf251

Sokratia Georgaka, William Geraint Morgans, Qian Zhao, Diego Sanchez Martinez, Amin Ali, Mohamed Ghafoor, Syed-Murtuza Baker, Robert G Bristow, Mudassar Iqbal, Magnus Rattray

引用次数: 0

Long-read whole-genome sequencing-based concurrent haplotyping and aneuploidy profiling of single cells

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-01 DOI: 10.1093/nar/gkaf247

Yan Zhao, Olga Tsuiko, Tatjana Jatsenko, Greet Peeters, Erika Souche, Mathilde Geysens, Eftychia Dimitriadou, Arne Vanhie, Karen Peeraer, Sophie Debrock, Hilde Van Esch, Joris Robert Vermeesch

{"title":"Long-read whole-genome sequencing-based concurrent haplotyping and aneuploidy profiling of single cells","authors":"Yan Zhao, Olga Tsuiko, Tatjana Jatsenko, Greet Peeters, Erika Souche, Mathilde Geysens, Eftychia Dimitriadou, Arne Vanhie, Karen Peeraer, Sophie Debrock, Hilde Van Esch, Joris Robert Vermeesch","doi":"10.1093/nar/gkaf247","DOIUrl":"https://doi.org/10.1093/nar/gkaf247","url":null,"abstract":"Long-read whole-genome sequencing (lrWGS) enhances haplotyping by providing more phasing information per read compared to short-read sequencing. However, its use for single-cell haplotype phasing remains underexplored. This proof-of-concept study examines lrWGS data from single cells for small variant (single nucleotide variant (SNV) and indel) and structural variation (SV) calling, as well as haplotyping, using the Genome in a Bottle (GIAB) Ashkenazi trio. lrWGS was performed on single-cell (1 cell) and multi-cell (10 cells) samples from the offspring. Chromosome-length haplotypes were obtained by leveraging both long reads and pedigree information. These haplotypes were further refined by replacing them with matched parental haplotypes. In single-cell and multi-cell samples, 92% and 98% of heterozygous SNVs, and 74% and 78% of heterozygous indels were accurately haplotyped. Applied to human embryos for preimplantation genetic testing (PGT), lrWGS demonstrated 100% consistency with array-based methods for detecting monogenic disorders, without requiring phasing references. Aneuploidies were accurately detected, with insights into the mechanistic origins of chromosomal abnormalities inferred from the parental unique allele fractions (UAFs). We show that lrWGS-based concurrent haplotyping and aneuploidy profiling of single cells provides an alternative to current PGT methods, with applications potential in areas such as cell-based prenatal diagnosis and animal and plant breeding.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"15 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744937","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

Fungal chromatin remodeler Isw1 modulates translation via regulating tRNA transcription

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-01 DOI: 10.1093/nar/gkaf225

Jing Wang, Yueqi Zhang, Jingrui Wang, Liuqin Wang, Binshan Li, Shuang Liu, Xuepeng Sun, Zhonghua Ma

{"title":"Fungal chromatin remodeler Isw1 modulates translation via regulating tRNA transcription","authors":"Jing Wang, Yueqi Zhang, Jingrui Wang, Liuqin Wang, Binshan Li, Shuang Liu, Xuepeng Sun, Zhonghua Ma","doi":"10.1093/nar/gkaf225","DOIUrl":"https://doi.org/10.1093/nar/gkaf225","url":null,"abstract":"Chromatin dynamics are essential for regulating DNA processes in response to environmental stimuli. Although ISWI-family enzymes are known to remodel chromatin by sliding nucleosomes in budding yeast, their functional roles and outputs in eukaryotes remain largely unknown. In this study, we investigated chromatin accessibility in the phytopathogenic fungus Fusarium graminearum treated with and without putrescine, a compound that rapidly induces the biosynthesis of the mycotoxin deoxynivalenol (DON). Putrescine globally alters chromatin accessibility, with the ATP-dependent chromatin remodeler FgIsw1 emerging as a key regulator. Unexpectedly, deletion of FgIsw1 did not affect the transcription of DON biosynthesis genes (Tri) but significantly disrupted transfer RNA (tRNA) transcription, leading to a dramatic decline in translation of DON biosynthesis enzymes. Mechanistically, FgIsw1 maintains nucleosome phasing in tRNA chromatin regions, ensuring efficient tRNA transcription. As a result, ΔFgIsw1 was unable to produce DON and lost its virulence on the host plant. These results highlight a novel role of chromatin remodelers in regulating protein translation through the control of tRNA transcription.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"75 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744931","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

N4-acetylcytidine coordinates with NP1 and CPSF5 to facilitate alternative RNA processing during the replication of minute virus of canines

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-04-01 DOI: 10.1093/nar/gkaf229

Xueyan Zhang, Shuangkang Qin, Fang Huang, Haizhou Liu, Jun Wang, Zhen Chen, Haojie Hao, Shuang Ding, Lishi Liu, Baocheng Yu, Yi Liu, Haibin Liu, Wuxiang Guan

{"title":"N4-acetylcytidine coordinates with NP1 and CPSF5 to facilitate alternative RNA processing during the replication of minute virus of canines","authors":"Xueyan Zhang, Shuangkang Qin, Fang Huang, Haizhou Liu, Jun Wang, Zhen Chen, Haojie Hao, Shuang Ding, Lishi Liu, Baocheng Yu, Yi Liu, Haibin Liu, Wuxiang Guan","doi":"10.1093/nar/gkaf229","DOIUrl":"https://doi.org/10.1093/nar/gkaf229","url":null,"abstract":"RNA modifications play crucial roles in RNA metabolism, structure, and functions. N4-acetylcytidine (ac4C) modifications have been shown to enhance stability and translation efficiency of messenger RNAs and viral RNAs. However, the relationship between ac4C and alternative RNA processing remains unexplored. Here, N-acetyltransferase 10 (NAT10) and its catalyzed ac4C modifications on minute virus of canines (MVC) were shown to regulate viral DNA replication and RNA processing, including both the alternative RNA splicing and polyadenylation. Through acRIP-seq and RedaC:T-seq, functional ac4C-modified residue 3311 was identified and characterized, which affected MVC RNA processing rather than altered the viral RNA stability. Ac4C modification at nt 3311 was revealed to participate in NP1-mediated viral RNA processing without influencing RNA affinity of NP1. Meanwhile, CPSF5 was identified to interact with NP1 and mediate viral RNA processing in an ac4C-dependent manner. Further in vitro assays showed that NP1 recruited CPSF5 to MVC RNAs, and the ac4C modification promoted specific binding of CPSF5 to the target region, which ensured precise alternative MVC RNA processing. This study not only reveals the functions of NAT10 and ac4C but also elucidates the mechanisms by which RNA modifications orchestrate MVC proteins and host factors for efficient viral replication and alternative RNA processing.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"34 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744943","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

Spatiotemporal dynamics of protamine–DNA condensation revealed by high-speed atomic force microscopy

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-03-24 DOI: 10.1093/nar/gkaf152

Goro Nishide, Keesiang Lim, Akiko Kobayashi, Yujia Qiu, Masaharu Hazawa, Toshio Ando, Yuki Okada, Richard W Wong

{"title":"Spatiotemporal dynamics of protamine–DNA condensation revealed by high-speed atomic force microscopy","authors":"Goro Nishide, Keesiang Lim, Akiko Kobayashi, Yujia Qiu, Masaharu Hazawa, Toshio Ando, Yuki Okada, Richard W Wong","doi":"10.1093/nar/gkaf152","DOIUrl":"https://doi.org/10.1093/nar/gkaf152","url":null,"abstract":"Protamines (PRMs) play a crucial role in sperm chromatin condensation, replacing histones to form nucleo–PRM structures, specifically PRM–DNA complexes. Despite their importance in reproduction, the detailed mechanisms underlying PRM-mediated DNA condensation have remained elusive. In this study, we employed high-speed atomic force microscopy (HS-AFM) to directly visualize the real-time binding dynamics of PRM to DNA under physiological conditions. Our HS-AFM observations reveal that PRM insertion initiating the formation of DNA coils. Further, we observed a heterogeneous spatial distribution of PRM-induced DNA looping. With continuous PRM addition, DNA progresses through a series of folding transitions, forming coiled-like structures that evolve into clockwise spirals, rod-shaped intermediates, and ultimately toroid-like nanostructures. Based on these real-time observations, we propose the CARD (Coil-Assembly-Rod-Doughnut) model to describe the stepwise process of toroid formation during DNA condensation. Our findings underscore the versatility of HS-AFM in capturing the spatiotemporal dynamics of PRM–DNA interactions and provide critical insights into the molecular mechanisms driving PRM-induced chromatin compaction. This study advances our understanding of sperm chromatin architecture and offers a framework for future research into chromatin organization, reproductive biology, and nucleic acid therapeutics.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"25 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677570","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