Nucleic Acids Research最新文献

A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei 一种可扩展的CRISPR- cas9基因编辑系统促进了疟疾寄生虫伯氏疟原虫的CRISPR筛选

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-23 DOI: 10.1093/nar/gkaf005

Thorey K Jonsdottir, Martina S Paoletta, Takahiro Ishizaki, Sophia Hernandez, Maria Ivanova, Alicia Herrera Curbelo, Paulina A Saiki, Martin Selinger, Debojyoti Das, Johan Henriksson, Ellen S C Bushell

{"title":"A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei","authors":"Thorey K Jonsdottir, Martina S Paoletta, Takahiro Ishizaki, Sophia Hernandez, Maria Ivanova, Alicia Herrera Curbelo, Paulina A Saiki, Martin Selinger, Debojyoti Das, Johan Henriksson, Ellen S C Bushell","doi":"10.1093/nar/gkaf005","DOIUrl":"https://doi.org/10.1093/nar/gkaf005","url":null,"abstract":"Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses a single cloning step to generate targeting vectors with 100-bp homology arms physically linked to a guide RNA (gRNA) that effectively integrate into the target locus. We show that PbHiT coupled with gRNA sequencing robustly recapitulates known knockout mutant phenotypes in pooled transfections. Furthermore, we provide an online resource of knockout and tagging designs to target the entire P. berghei genome and scale-up vector production using a pooled ligation approach. This work presents for the first time a tool for high-throughput CRISPR screens in Plasmodium for studying the parasite’s biology at scale.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"33 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020617","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

‘Splice-at-will’ Cas12a crRNA engineering enabled direct quantification of ultrashort RNAs “随意剪接”Cas12a crRNA工程实现了超短rna的直接定量

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkaf002

Xinrui Fei, Chao Lei, Wei Ren, Chenghui Liu

{"title":"‘Splice-at-will’ Cas12a crRNA engineering enabled direct quantification of ultrashort RNAs","authors":"Xinrui Fei, Chao Lei, Wei Ren, Chenghui Liu","doi":"10.1093/nar/gkaf002","DOIUrl":"https://doi.org/10.1093/nar/gkaf002","url":null,"abstract":"We present a robust ‘splice-at-will’ CRISPR RNA (crRNA) engineering mechanism that overcomes the limitations of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system in directly detecting ultrashort RNAs. In this strategy, an intact Cas12a crRNA can be split from almost any site of the spacer region to obtain a truncated crRNA (tcrRNA) that cannot activate Cas12a even after binding an auxiliary DNA activator. While splicing tcrRNAs with a moiety of ultrashort RNA, the formed combination can work together to activate Cas12a efficiently, enabling ‘splice-at-will’ crRNA engineering. Importantly, the ‘splice-at-will’ crRNA exhibits almost the same trans-cleavage activation efficiency as that of a conventional intact crRNA. Therefore, by rationally designing a DNA auxiliary activator with a conserved tcrRNA-complementary sequence and an arbitrary short RNA-of-interest recognition domain, a general sensing system is established that directly utilizes traditional DNA-activated Cas12a to detect ultrashort RNAs. This ‘splice-at-will’ crRNA engineering strategy could faithfully detect ultrashort RNA sequences as short as 6–8 nt, which cannot be achieved by conventional Cas12a and Cas13a systems. Additionally, through flexible splicing site design, our method can precisely distinguish single-base differences in microRNA and other short RNA sequences. This work has significantly expanded the Cas12a-based diagnostic toolbox and opened new avenues for ultrashort RNA detection.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"74 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990081","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 SARS-CoV-2 nucleocapsid protein interferes with the full enzymatic activation of UPF1 and its interaction with UPF2 SARS-CoV-2核衣壳蛋白干扰UPF1的全酶激活及其与UPF2的相互作用

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkaf010

Veronica Nuccetelli, Makram Mghezzi-Habellah, Séverine Deymier, Armelle Roisin, Francine Gérard-Baraggia, Cecilia Rocchi, Pierre-Damien Coureux, Patrice Gouet, Andrea Cimarelli, Vincent Mocquet, Francesca Fiorini

{"title":"The SARS-CoV-2 nucleocapsid protein interferes with the full enzymatic activation of UPF1 and its interaction with UPF2","authors":"Veronica Nuccetelli, Makram Mghezzi-Habellah, Séverine Deymier, Armelle Roisin, Francine Gérard-Baraggia, Cecilia Rocchi, Pierre-Damien Coureux, Patrice Gouet, Andrea Cimarelli, Vincent Mocquet, Francesca Fiorini","doi":"10.1093/nar/gkaf010","DOIUrl":"https://doi.org/10.1093/nar/gkaf010","url":null,"abstract":"The nonsense-mediated mRNA decay (NMD) pathway triggers the degradation of defective mRNAs and governs the expression of mRNAs with specific characteristics. Current understanding indicates that NMD is often significantly suppressed during viral infections to protect the viral genome. In numerous viruses, this inhibition is achieved through direct or indirect interference with the RNA helicase UPF1, thereby promoting viral replication and enhancing pathogenesis. In this study, we employed biochemical, biophysical assays and cellular investigations to explore the interplay between UPF1 and the nucleocapsid (Np) protein of SARS-CoV-2. We evaluated their direct interaction and its impact on inhibiting cellular NMD. Furthermore, we characterized how this interaction affects UPF1’s enzymatic function. Our findings demonstrate that Np inhibits the unwinding activity of UPF1 by physically obstructing its access to structured nucleic acid substrates. Additionally, we showed that Np binds directly to UPF2, disrupting the formation of the UPF1/UPF2 complex essential for NMD progression. Intriguingly, our research also uncovered a surprising pro-viral role of UPF1 and an antiviral function of UPF2. These results unveil a novel, multi-faceted mechanism by which SARS-CoV-2 evades the host’s defenses and manipulates cellular components. This underscores the potential therapeutic strategy of targeting Np-UPF1/UPF2 interactions to treat COVID-19.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"151 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990083","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-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide 胶质母细胞瘤药物替莫唑胺中 O6-甲基鸟嘌呤的单核苷酸分辨率基因组图谱

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkae1320

Jasmina Kubitschek, Vakil Takhaveev, Cécile Mingard, Martha I Rochlitz, Patricia B Reinert, Giulia Keller, Tom Kloter, Raúl Fernández Cereijo, Sabrina M Huber, Maureen McKeague, Shana J Sturla

{"title":"Single-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide","authors":"Jasmina Kubitschek, Vakil Takhaveev, Cécile Mingard, Martha I Rochlitz, Patricia B Reinert, Giulia Keller, Tom Kloter, Raúl Fernández Cereijo, Sabrina M Huber, Maureen McKeague, Shana J Sturla","doi":"10.1093/nar/gkae1320","DOIUrl":"https://doi.org/10.1093/nar/gkae1320","url":null,"abstract":"Temozolomide kills cancer cells by forming O6-methylguanine (O6-MeG), which leads to cell cycle arrest and apoptosis. However, O6-MeG repair by O6-methylguanine-DNA methyltransferase (MGMT) contributes to drug resistance. Characterizing genomic profiles of O6-MeG could elucidate how O6-MeG accumulation is influenced by repair, but there are no methods to map genomic locations of O6-MeG. Here, we developed an immunoprecipitation- and polymerase-stalling-based method, termed O6-MeG-seq, to locate O6-MeG across the whole genome at single-nucleotide resolution. We analyzed O6-MeG formation and repair across sequence contexts and functional genomic regions in relation to MGMT expression in a glioblastoma-derived cell line. O6-MeG signatures were highly similar to mutational signatures from patients previously treated with temozolomide. Furthermore, MGMT did not preferentially repair O6-MeG with respect to sequence context, chromatin state or gene expression level, however, may protect oncogenes from mutations. Finally, we found an MGMT-independent strand bias in O6-MeG accumulation in highly expressed genes. These data provide high resolution insight on how O6-MeG formation and repair are impacted by genome structure and nucleotide sequence. Further, O6-MeG-seq is expected to enable future studies of DNA modification signatures as diagnostic markers for addressing drug resistance and preventing secondary cancers.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"8 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990261","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

DesiRNA: structure-based design of RNA sequences with a replica exchange Monte Carlo approach 基于结构的RNA序列设计与复制交换蒙特卡罗方法

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkae1306

Tomasz K Wirecki, Grzegorz Lach, Nagendar Goud Badepally, S Naeim Moafinejad, Farhang Jaryani, Gaja Klaudel, Kalina Nec, Eugene F Baulin, Janusz M Bujnicki

{"title":"DesiRNA: structure-based design of RNA sequences with a replica exchange Monte Carlo approach","authors":"Tomasz K Wirecki, Grzegorz Lach, Nagendar Goud Badepally, S Naeim Moafinejad, Farhang Jaryani, Gaja Klaudel, Kalina Nec, Eugene F Baulin, Janusz M Bujnicki","doi":"10.1093/nar/gkae1306","DOIUrl":"https://doi.org/10.1093/nar/gkae1306","url":null,"abstract":"Designing RNA sequences that form a specific structure remains a challenge. Current computational methods often struggle with the complexity of RNA structures, especially when considering pseudoknots or restrictions related to RNA function. We developed DesiRNA, a computational tool for the design of RNA sequences based on the Replica Exchange Monte Carlo approach. It finds sequences that minimize a multiobjective scoring function, fulfill user-defined constraints and minimize the violation of restraints. DesiRNA handles pseudoknots, designs RNA–RNA complexes and sequences with alternative structures, prevents oligomerization of monomers, prevents folding into undesired structures and allows users to specify nucleotide composition preferences. In benchmarking tests, DesiRNA with a default simple scoring function solved all 100 puzzles in the Eterna100 benchmark within 24 h, outperforming all existing RNA design programs. With its ability to address complex RNA design challenges, DesiRNA holds promise for a range of applications in RNA research and therapeutic development.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"18 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990084","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

Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish Cre-Lox microRNA递送技术优化用于斑马鱼诱导microRNA和基因沉默研究

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkaf004

Fangfei Guo, Alisha Tromp, Haitao Wang, Thomas E Hall, Jean Giacomotto

{"title":"Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish","authors":"Fangfei Guo, Alisha Tromp, Haitao Wang, Thomas E Hall, Jean Giacomotto","doi":"10.1093/nar/gkaf004","DOIUrl":"https://doi.org/10.1093/nar/gkaf004","url":null,"abstract":"While many genetic tools exist for zebrafish, this animal model still lacks robust gene-silencing and microRNA-delivery technologies enabling spatio-temporal control and traceability. We have recently demonstrated that engineered pri-miR backbones can trigger stable gene knockdown and/or express microRNA(s) of choice in this organism. However, this miRNA-expressing technology presents important limitations. First, to trigger potent knockdown(s), multiple synthetic-miRNAs must be expressed simultaneously, compromising the co-expression of fluorescent marker(s) and knockdown traceability. Second, when gene(s) knockdown triggers significant phenotypes, like homozygous mutants with severe early phenotypes, it is difficult, if not impossible, to maintain transgenic carriers. To solve these problems and provide a mature RNAi and microRNA-delivery technology, we have generated new RNAi reagents and an inducible delivery system based on the Cre/Lox technology. This system allows the creation of asymptomatic/silent carriers, easing the production of embryos with potent knockdowns that can be traced and spatiotemporally controlled. We further demonstrated the utility of this approach by establishing novel inducible and tissue-specific models of spinal muscular atrophy, opening new avenues for studying smn1-gene function and pathogenicity. All in all, these materials and techniques will be invaluable in studying microRNA biology and in modelling or tackling conditions in which gene dosage is key.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"13 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990085","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 integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis 一种精确检测HERV-K HML-2转录和蛋白合成的综合方法

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-20 DOI: 10.1093/nar/gkaf011

Charles Gleason, Sandra N Terry, Matthew M Hernandez, Samson Jacob, David Fenyo, Jeffrey R Johnson, Gintaras Deikus, Nancy Francoeur, Aana Hahn, Robert Sebra, Dmitriy Zamarin, Henrik Molina, Viviana Simon, Lubbertus C F Mulder

{"title":"An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis","authors":"Charles Gleason, Sandra N Terry, Matthew M Hernandez, Samson Jacob, David Fenyo, Jeffrey R Johnson, Gintaras Deikus, Nancy Francoeur, Aana Hahn, Robert Sebra, Dmitriy Zamarin, Henrik Molina, Viviana Simon, Lubbertus C F Mulder","doi":"10.1093/nar/gkaf011","DOIUrl":"https://doi.org/10.1093/nar/gkaf011","url":null,"abstract":"Human endogenous retroviruses (HERVs) occupy a large portion of the human genome. Most HERVs are transcriptionally silent, but they can be reactivated during pathological states such as viral infection and certain cancers. The HERV-K HML-2 clade includes elements that recently integrated have in the human germ line and often contain intact open reading frames that possibly support peptide and protein expression. Understanding HERV–K-host interactions and their potential as biomarkers is problematic due to the high similarity among different elements. Previously, we described a long-read single molecule real-time sequencing (PacBio) strategy to analyze HERV-K RNA expression profiles in different cell types. However, identifying HERV-K HML-2 proteins accurately is difficult without robust and reliable methods and reagents. Here we present a new approach to characterize the HML-2 elements that (a) are being translated and (b) produce enough protein to be detected and identified by mass spectrometry. Our data reveal that RNA expression profiling alone cannot accurately predict which HML-2 elements are responsible for protein production, as we observe several differences between the highest expressed RNAs and the elements that are the predominant source of HERV-K HML-2 protein synthesis. These studies represent an important advance toward untangling the complexity of HERV–K-host interactions.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"57 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990082","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

Nonlinear regulatory dynamics of bacterial restriction-modification systems modulates horizontal gene transfer susceptibility 细菌限制性修饰系统的非线性调控动力学调节水平基因转移易感性

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-16 DOI: 10.1093/nar/gkae1322

Magdalena Djordjevic, Lidija Zivkovic, Hong-Yu Ou, Marko Djordjevic

{"title":"Nonlinear regulatory dynamics of bacterial restriction-modification systems modulates horizontal gene transfer susceptibility","authors":"Magdalena Djordjevic, Lidija Zivkovic, Hong-Yu Ou, Marko Djordjevic","doi":"10.1093/nar/gkae1322","DOIUrl":"https://doi.org/10.1093/nar/gkae1322","url":null,"abstract":"Type II restriction-modification (R–M) systems play a pivotal role in bacterial defense against invading DNA, influencing the spread of pathogenic traits. These systems often involve coordinated expression of a regulatory protein (C) with restriction (R) enzymes, employing complex feedback loops for regulation. Recent studies highlight the crucial balance between R and M enzymes in controlling horizontal gene transfer (HGT). This manuscript introduces a mathematical model reflecting R–M system dynamics, informed by biophysical evidence, to minimize reliance on arbitrary parameters. Our analysis clarifies the observed variations in M-to-R ratios, emphasizing the regulatory role of the C protein. We analytically derived a stability diagram for C-regulated R–M systems, offering a more straightforward analysis method over traditional numerical approaches. Our findings reveal conditions leading to both monostability and bistability, linking changes in the M-to-R ratio to factors like cell division timing and plasmid replication rates. These variations may link adjusting defense against phage infection, or the acquisition of new genes such as antibiotic resistance determinants, to changing physiological conditions. We also performed stochastic simulations to show that system regulation may significantly increase M-to-R ratio variability, providing an additional mechanism to generate heterogeneity in bacterial population.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"205 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987290","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

Distinct structural and functional heterochromatin partitioning of lamin B1 and lamin B2 revealed using genome-wide nicking enzyme epitope targeted DNA sequencing 利用全基因组缺口酶表位靶向DNA测序揭示了层合蛋白B1和层合蛋白B2的不同结构和功能异染色质分配

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-16 DOI: 10.1093/nar/gkae1317

Sagnik Sen, Pierre-Olivier Estève, Karthikeyan Raman, Julie Beaulieu, Hang Gyeong Chin, George R Feehery, Udayakumar S Vishnu, Shuang-yong Xu, James C Samuelson, Sriharsa Pradhan

{"title":"Distinct structural and functional heterochromatin partitioning of lamin B1 and lamin B2 revealed using genome-wide nicking enzyme epitope targeted DNA sequencing","authors":"Sagnik Sen, Pierre-Olivier Estève, Karthikeyan Raman, Julie Beaulieu, Hang Gyeong Chin, George R Feehery, Udayakumar S Vishnu, Shuang-yong Xu, James C Samuelson, Sriharsa Pradhan","doi":"10.1093/nar/gkae1317","DOIUrl":"https://doi.org/10.1093/nar/gkae1317","url":null,"abstract":"Gene expression is regulated by chromatin DNA methylation and other features, including histone post-translational modifications (PTMs), chromatin remodelers and transcription factor occupancy. A complete understanding of gene regulation will require the mapping of these chromatin features in small cell number samples. Here we describe a novel genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq). NEED-seq offers antibody-targeted controlled nicking by Nt.CviPII-pGL fusion to study specific protein–DNA complexes in formaldehyde fixed cells, allowing for both visual and genomic resolution of epitope bound chromatin. When applied to nuclei, NEED-seq yielded genome-wide profile of chromatin-associated proteins and histone PTMs. Additionally, NEED-seq of lamin B1 and B2 demonstrated their association with heterochromatin. Lamin B1- and B2-associated domains (LAD) segregated to three different states, and states with stronger LAD correlated with heterochromatic marks. Hi-C analysis displayed A and B compartment with equal lamin B1 and B2 distribution, although methylated DNA remained high in B compartment. LAD clustering with Hi-C resulted in subcompartments, with lamin B1 and B2 partitioning to facultative and constitutive heterochromatin, respectively, and were associated with neuronal development. Thus, lamin B1 and B2 show structural and functional partitioning in mammalian nucleus.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"30 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987291","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

Embedding a ribonuclease in the spore crust couples gene expression to spore development in Bacillus subtilis 在枯草芽孢杆菌孢子壳中嵌入核糖核酸酶，将基因表达与孢子发育结合起来

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-01-16 DOI: 10.1093/nar/gkae1301

Alexandre D’Halluin, Laetitia Gilet, Armand Lablaine, Olivier Pellegrini, Mónica Serrano, Anastasia Tolcan, Magali Ventroux, Sylvain Durand, Marion Hamon, Adriano O Henriques, Rut Carballido-López, Ciarán Condon

{"title":"Embedding a ribonuclease in the spore crust couples gene expression to spore development in Bacillus subtilis","authors":"Alexandre D’Halluin, Laetitia Gilet, Armand Lablaine, Olivier Pellegrini, Mónica Serrano, Anastasia Tolcan, Magali Ventroux, Sylvain Durand, Marion Hamon, Adriano O Henriques, Rut Carballido-López, Ciarán Condon","doi":"10.1093/nar/gkae1301","DOIUrl":"https://doi.org/10.1093/nar/gkae1301","url":null,"abstract":"Faced with nutritional stress, some bacteria form endospores capable of enduring extreme conditions for long periods of time; yet the function of many proteins expressed during sporulation remains a mystery. We identify one such protein, KapD, as a 3′-exoribonuclease expressed under control of the mother cell-specific transcription factors SigE and SigK in Bacillus subtilis. KapD dynamically assembles over the spore surface through a direct interaction with the major crust protein CotY. KapD catalytic activity is essential for normal adhesiveness of spore surface layers. We identify the sigK mRNA as a key KapD substrate and and show that the stability of this transcript is regulated by CotY-mediated sequestration of KapD. SigK is tightly controlled through excision of a prophage-like element, transcriptional regulation and the removal of an inhibitory pro-sequence. Our findings uncover a fourth, post-transcriptional layer of control of sigK expression that couples late-stage gene expression in the mother cell to spore morphogenesis.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"69 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987522","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