Nucleic Acids Research最新文献_第5页

A conserved nuclease facilitates environmental DNA uptake 一个保守的核酸酶促进环境DNA的摄取

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-27 DOI: 10.1093/nar/gkaf443

Juri Hanßmann, Jan Pané-Farré, Milena Meiser, Mathias Girbig, Lifei Fu, M Gregor Madej, Franziska L Sendker, Clemens Thölken, Marcus Lechner, Christine Ziegler, Georg K A Hochberg, Gert Bange, Martin Thanbichler, Rebecca Hinrichs

{"title":"A conserved nuclease facilitates environmental DNA uptake","authors":"Juri Hanßmann, Jan Pané-Farré, Milena Meiser, Mathias Girbig, Lifei Fu, M Gregor Madej, Franziska L Sendker, Clemens Thölken, Marcus Lechner, Christine Ziegler, Georg K A Hochberg, Gert Bange, Martin Thanbichler, Rebecca Hinrichs","doi":"10.1093/nar/gkaf443","DOIUrl":"https://doi.org/10.1093/nar/gkaf443","url":null,"abstract":"Bacteria acquire new traits through the uptake of genetic material from the environment, a process requiring DNA processing. However, the molecular inventory mediating this process is far from being completely understood. Here, we identify YhaM in Bacillus subtilis as a conserved 3′-deoxyribonuclease essential for the uptake and processing of genetic information in the form of single-stranded DNA. Our results show that YhaM assembles into hexamers in the presence of divalent cations, enhancing substrate binding, which is achieved through its conserved oligonucleotide-binding domain. Cells lacking YhaM show a severe defect in the uptake of plasmids and genomic DNA, but the transduction of double-stranded DNA by the phage SPP1 remains unaffected. These findings highlight a critical role of YhaM in single-stranded DNA maturation during natural transformation. Importantly, this function is conserved in various Gram-positive human pathogens such as Staphylococcus aureus, suggesting that it could contribute to the spread of antibiotic resistance.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"7 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145492","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 role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex 多价性在821蛋白2 （ETO2）与核小体重塑和去乙酰化酶（NuRD）复合体的关联中的作用

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-27 DOI: 10.1093/nar/gkaf439

Glory Dan-Dukor, Shengzhe Shang, Gage O Leighton, Christopher R Travis, Timothy D Schwochert, Parnika Agrawal, Oyindamola Ajasa, Torry Li, Marcey L Waters, Gordon D Ginder, David C Williams

{"title":"The role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex","authors":"Glory Dan-Dukor, Shengzhe Shang, Gage O Leighton, Christopher R Travis, Timothy D Schwochert, Parnika Agrawal, Oyindamola Ajasa, Torry Li, Marcey L Waters, Gordon D Ginder, David C Williams","doi":"10.1093/nar/gkaf439","DOIUrl":"https://doi.org/10.1093/nar/gkaf439","url":null,"abstract":"Over the past 50 years, research has uncovered the co-regulatory proteins and complexes that silence the expression of the γ-globin gene in a developmental stage-specific manner. Recent research expanded the list of these regulatory factors by showing that the eight twenty-one protein 2 (ETO2) helps recruit the nucleosome remodeling and deacetylase (NuRD) complex to the globin locus. Furthermore, ETO2 regulates hematopoietic differentiation and is a potential therapeutic target for acute leukemia. In this work, we identify critical interactions between ETO2 and the GATA Zn finger domain containing the 2A (GATAD2A) component of NuRD. The ETO2 nervy homology region 4 (NHR4) domain interacts with multiple polyproline-leucine motifs within GATAD2A. We demonstrate that oligomerization of the ETO2 nervy homology region 3 (NHR3) enhances its affinity for peptides containing at least two polyproline-leucine motifs. Replacing the native motifs from GATAD2A with a higher-affinity sequence from known-binder N-CoR markedly enhances binding affinity, yielding a peptide that disrupts the interaction between ETO2 and target proteins. Enforced peptide expression elevates γ-globin expression levels and induces differentiation of HUDEP-2 and K562 cells. These findings provide insight into ETO2-mediated recruitment of co-regulatory proteins and yield a novel approach for ETO2 inhibition through multivalent binding of the NHR4 domain.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"97 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145491","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

Transcription regulation by RNA-induced structural strain in duplex DNA. rna诱导的双链DNA结构应变的转录调控。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf429

Aura Cencini,Graziano Rilievo,Alessandro Cecconello,Federica Tonolo,Massimiliano Babbucci,Enrico Negrisolo,Massimiliano Magro,Fabio Vianello

{"title":"Transcription regulation by RNA-induced structural strain in duplex DNA.","authors":"Aura Cencini,Graziano Rilievo,Alessandro Cecconello,Federica Tonolo,Massimiliano Babbucci,Enrico Negrisolo,Massimiliano Magro,Fabio Vianello","doi":"10.1093/nar/gkaf429","DOIUrl":"https://doi.org/10.1093/nar/gkaf429","url":null,"abstract":"Non-coding RNAs belong to a heterogenous family that, among other functions, acts as a biomolecular regulator of gene expression. In particular, lncRNAs, which are estimated to be as numerous as coding RNAs in humans, are thought to interact with genomic DNA to form triple helices. However, experimental evidence of their involvement with processes, such as chromatin structure dynamics or RNA transcription, is still missing. Here, a mechanism of transcription enhancement/inhibition is described, where hybrid RNA-DNA triplexes regulate transcription rates in Escherichia coli promoter-based designed architectures. Sequences associated with triplexes were identified in a library of bacterial promoters and characterized in vitro, followed by a synthetic biology approach to verify their ability to control transcription and translation. A model of the triplex-promoter complex was produced showing that transcription enhancement is due to a distortion of the duplex DNA as a consequence of its conjugation with RNA in the triplex assembly. These results point at a mechanism of RNA function that is still unknown and could be common in more complex organisms, such as metazoans including mammals, where non-coding RNAs are more abundant and are believed to play a fundamental role in determining hetero/euchromatin and transcription modulation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"20 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114110","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 antibiotic-responsive regulator orchestrates chronic-to-acute virulence switch in Pseudomonas aeruginosa. 在铜绿假单胞菌中，抗生素反应性调节因子协调慢性到急性毒力转换。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf471

Xinbo Wang, Guizhen Li, Yuzheng Zou, Huiluo Cao, Lisheng Liao, Xiaofan Zhou, Lian-Hui Zhang, Zeling Xu

{"title":"An antibiotic-responsive regulator orchestrates chronic-to-acute virulence switch in Pseudomonas aeruginosa.","authors":"Xinbo Wang, Guizhen Li, Yuzheng Zou, Huiluo Cao, Lisheng Liao, Xiaofan Zhou, Lian-Hui Zhang, Zeling Xu","doi":"10.1093/nar/gkaf471","DOIUrl":"10.1093/nar/gkaf471","url":null,"abstract":"Misuse and overuse of antibiotics have led to the rapid emergence of antibiotic-resistant superbugs. In addition, evidence is emerging that antibiotic exposure could impose substantial influence on bacterial virulence, but the underlying mechanisms remain poorly understood. Here, we discovered a highly conserved aminoglycoside-responsive regulator, AmgR, that inversely modulates the production of destructive toxins [pyocyanin (PYO) and protease] and the inter-bacterial competition weapon [type VI secretion system (H1-T6SS)], which are the signature virulence factors involved in acute and chronic infections, respectively, in Pseudomonas aeruginosa. We demonstrated that AmgR positively regulates PYO and protease productions by directly activating the transcription of their biosynthetic genes and negatively regulates H1-T6SS indirectly through the quorum sensing regulator PqsR. Importantly, we showed that AmgR can be induced by sub-inhibitory concentrations of aminoglycoside antibiotics to trigger the bacterial chronic-to-acute virulence switch, by promoting P.aeruginosa to withdraw from production of the chronic infection-associated virulence factor H1-T6SS to gear up for generation of acute infection related toxins PYO and protease. This study highlights the risks of improper antibiotic usage not only in elevating antibiotic resistance but also in reprogramming bacterial virulence to exacerbate disease dissemination and acute lethality, providing critical insights for the optimization of antibiotic therapies.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 10","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216478","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

Correction to 'Molecular mechanisms of extrachromosomal circular DNA formation'. 更正“染色体外环状DNA形成的分子机制”。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf491

引用次数: 0

Preparation of topoisomers of short circular dsDNA with defined linking number by accurate topological control. 通过精确的拓扑控制制备具有确定连接数的短圆双链dna拓扑异构体。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf456

Mengqin Liu, Ziyi Wang, Ran An, Angda Li, Xingguo Liang

{"title":"Preparation of topoisomers of short circular dsDNA with defined linking number by accurate topological control.","authors":"Mengqin Liu, Ziyi Wang, Ran An, Angda Li, Xingguo Liang","doi":"10.1093/nar/gkaf456","DOIUrl":"10.1093/nar/gkaf456","url":null,"abstract":"Short DNA catenanes [circular double-stranded DNA (dsDNA)] have attracted considerable interest for constructing nanostructures and nanomachines, as well as understanding DNA topology. The study of topoisomers of a circular dsDNA with a definite linking number (Lk) is essential but very difficult for simplifying the complex problems about DNA topology. The topoisomers are difficult to prepare, especially in the case that two strands are completely complementary. In this study, using a model system, we prepared all eight topoisomers (Lk0-Lk7) of a 79-bp-long circular dsDNA (8-14 nm in size) by utilizing aid-DNA to prevent undesired hybridization. By rapid ligation before strand displacement, high selectivity (>75%) for most topoisomers (31% for Lk1) was achieved under the strict topological control. All eight topoisomers with high purity were obtained after purification. Using a gel shift assay with Z-DNA-specific binding proteins, as well as by circular dichroism chromatography and enzymatic digestion, it was found that Z-DNA forms for topoisomers Lk0-Lk6, and Lk0-Lk5 can be converted to Lk6 by topoisomerase I. The approach developed in this study can significantly contribute to DNA or RNA topology, particularly the effect of topological constraints on DNA structures and functions.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 10","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160622","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

SRSF10 regulates oligodendrocyte differentiation during mouse central nervous system development by modulating pre-mRNA splicing. SRSF10通过调节pre-mRNA剪接调节小鼠中枢神经系统发育过程中少突胶质细胞的分化。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf455

Yawei Mu, Zixuan Wei, Menghan Sun, Junjie Li, Yi Jiang, Hanyang Jiang, Ankangzhi Ma, Cuiqing Zhu, Xianhua Chen

{"title":"SRSF10 regulates oligodendrocyte differentiation during mouse central nervous system development by modulating pre-mRNA splicing.","authors":"Yawei Mu, Zixuan Wei, Menghan Sun, Junjie Li, Yi Jiang, Hanyang Jiang, Ankangzhi Ma, Cuiqing Zhu, Xianhua Chen","doi":"10.1093/nar/gkaf455","DOIUrl":"10.1093/nar/gkaf455","url":null,"abstract":"We characterized the role and regulation mechanism of a pre-mRNA splicing factor, SRSF10, in the development of oligodendrocyte lineage cells (OLCs) and the myelination process during mouse central nervous system (CNS) development. We found that depletion of SRSF10 specifically in OLCs induces hypomyelination and a decrease in OLCs in the developing mouse CNS, whereas depletion of SRSF10 only in differentiated OLCs does not significantly affect these processes. More detailed in vivo and in vitro analyses revealed that SRSF10 primarily regulates the earlier differentiation stages of OLCs, while the proliferation and apoptosis of OLCs were not affected. Mechanistically, RNA-seq and RIP-Seq transcript analyses identified a series of genes whose alternative splicing (AS) was directly regulated by SRSF10. Among these genes, compensating for the AS phenotype of Myo5a using antisense oligonucleotides (ASOs) reversed the inhibition of OLCs differentiation induced by SRSF10 depletion. In summary, we revealed for the first time that SRSF10 is a key regulator in the early differentiation of OLCs, likely via modulating the AS patterns of target genes such as Myo5a. This research provides significant implications for understanding OLC development and exploring potential therapeutic strategies for dysmyelination-related diseases.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 10","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174286","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

Expanding the σ54-dependent transcription process with orthogonal designs. 用正交设计扩展σ54依赖性转录过程。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf442

Yiheng Liu,Shuyi Cai,Ziyi Zhang,Zhuoting Xie,Chenyue Guo,Yi-Ping Wang,Jianguo Yang

{"title":"Expanding the σ54-dependent transcription process with orthogonal designs.","authors":"Yiheng Liu,Shuyi Cai,Ziyi Zhang,Zhuoting Xie,Chenyue Guo,Yi-Ping Wang,Jianguo Yang","doi":"10.1093/nar/gkaf442","DOIUrl":"https://doi.org/10.1093/nar/gkaf442","url":null,"abstract":"The significance of orthogonal gene expression lies in its ability to ensure consistent and predictable operation of genetic pathways in synthetic biology. In bacteria, σ factors are responsible for promoter recognition, where the recognition pattern of σ54 is distinct from that of σ70. Moreover, σ54-dependent promoters require bacterial enhancer-binding proteins (bEBPs) for transcription initiation, which are stringently regulated and strongly activated. Thus, σ54 appears to be a promising candidate for orthogonal designs. In this study, through knowledge-based screening and rewiring of the RpoN box in σ54, together with its partnered promoter, we identified three sets of orthogonal expression systems based on σ54-R456H, R456Y, and R456L, with different promoter preferences and ideal mutual orthogonality toward each other and the native σ54. The orthogonality is transferable, as specific transcription via σ54-R456H was demonstrated in three non-model bacteria. When combined with different bEBPs, the system can be employed to control orthogonal downstream output in response to environmental or chemical signals. The orthogonal σ54 factors proved to be capable of orthogonalizing complex biological pathways and genetic circuits. Therefore, the orthogonal transcription system will contribute to the expansion of synthetic biology toolkits, thereby providing reliable and diversified gene expression in a wide range of hosts.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"17 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114108","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

Single-cell imaging of N4-acetylcytidine-modified RNA using fluorine metabolic labeling mediated proximity ligation assay. 使用氟代谢标记介导的接近连接法对n4 -乙酰胞苷修饰RNA的单细胞成像。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf464

Qi Wang, Yuhao Du, Shen Yan, Ziang Lu, Yongling Tang, Feng Xiao, Fuling Zhou, Xiang Zhou

引用次数: 0

Compromised two-start zigzag chromatin folding in immature mouse retina cells driven by irregularly spaced nucleosomes with short DNA linkers. 由具有短DNA连接体的不规则间隔核小体驱动的未成熟小鼠视网膜细胞中两起点之字形染色质折叠受损。

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-05-22 DOI: 10.1093/nar/gkaf457

Brianna Kable, Stephanie Portillo-Ledesma, Evgenya Y Popova, Nathan Jentink, Matthew Swulius, Zilong Li, Tamar Schlick, Sergei A Grigoryev

{"title":"Compromised two-start zigzag chromatin folding in immature mouse retina cells driven by irregularly spaced nucleosomes with short DNA linkers.","authors":"Brianna Kable, Stephanie Portillo-Ledesma, Evgenya Y Popova, Nathan Jentink, Matthew Swulius, Zilong Li, Tamar Schlick, Sergei A Grigoryev","doi":"10.1093/nar/gkaf457","DOIUrl":"10.1093/nar/gkaf457","url":null,"abstract":"The formation of condensed heterochromatin is critical for establishing cell-specific transcriptional programs. To reveal structural transitions underlying heterochromatin formation in maturing mouse rod photoreceptors, we apply cryo-electron microscopy (cryo-EM) tomography, AI-assisted denoising, and molecular modeling. We find that chromatin isolated from immature retina cells contains many closely apposed nucleosomes with extremely short or absent nucleosome linkers, which are inconsistent with the typical two-start zigzag chromatin folding. In mature retina cells, the fraction of short-linker nucleosomes is much lower, supporting stronger chromatin compaction. By cryo-EM-assisted nucleosome interaction capture, we observe that chromatin in immature retina is enriched with i ± 1 interactions, while chromatin in mature retina contains predominantly i ± 2 interactions typical of the two-start zigzag. By mesoscale modeling and computational simulation, we clarify that the unusually short linkers typical of immature retina are sufficient to inhibit the two-start zigzag and chromatin compaction by the interference of very short linkers with linker DNA stems. We propose that this short linker composition renders nucleosome arrays more open in immature retina and that, as the linker DNA length increases in mature retina, chromatin becomes globally condensed via tight zigzag folding. This mechanism may be broadly utilized to introduce higher chromatin folding entropy for epigenomic plasticity.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 10","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216479","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