Nucleic Acids Research最新文献_第4页

gwSPADE: gene frequency-weighted reference-free deconvolution in spatial transcriptomics. 空间转录组学中的基因频率加权无参考反褶积。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf966

Aoqi Xie,Nina G Steele,Yuehua Cui

{"title":"gwSPADE: gene frequency-weighted reference-free deconvolution in spatial transcriptomics.","authors":"Aoqi Xie,Nina G Steele,Yuehua Cui","doi":"10.1093/nar/gkaf966","DOIUrl":"https://doi.org/10.1093/nar/gkaf966","url":null,"abstract":"Most spatial transcriptomics (ST) technologies (e.g. 10× Visium) operate at the multicellular level, where each spatial location often contains a mixture of cells with heterogeneous cell types. Thus, effective deconvolution of cell type compositions is critical for downstream analysis. Although reference-based deconvolution methods have been proposed, they depend on the availability of reference data, which may not always be accessible. Additionally, within a deconvolved cell type, cellular heterogeneity may still exist, requiring further deconvolution to uncover finer structures for a better understanding of this complexity. Here, we present gwSPADE, a gene frequency-weighted reference-free SPAtial DEconvolution method for ST data. gwSPADE requires only the gene count matrix and utilizes appropriate weighting schemes within a topic model to accurately recover cell type transcriptional profiles and their proportions at each spatial location, without relying on external single-cell reference information. In various simulations and real data analyses, gwSPADE demonstrates scalability across various platforms and shows superior performance over existing reference-free deconvolution methods such as STdeconvolve.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"64 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140240","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

A multi-dentate, cooperative interaction between endo- and exo-ribonucleases within the bacterial RNA degradosome. 细菌RNA降解体内内、外核糖核酸酶之间多齿状的合作相互作用。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf960

Giulia Paris, Kai Katsuya-Gaviria, Hannah Clarke, Margaret Johncock, Tom Dendooven, Aleksei Lulla, Ben F Luisi

{"title":"A multi-dentate, cooperative interaction between endo- and exo-ribonucleases within the bacterial RNA degradosome.","authors":"Giulia Paris, Kai Katsuya-Gaviria, Hannah Clarke, Margaret Johncock, Tom Dendooven, Aleksei Lulla, Ben F Luisi","doi":"10.1093/nar/gkaf960","DOIUrl":"10.1093/nar/gkaf960","url":null,"abstract":"In Escherichia coli and numerous other bacteria, two of the principal enzymes mediating messenger RNA decay and RNA processing-RNase E, an endoribonuclease, and polynucleotide phosphorylase (PNPase), an exoribonuclease-assemble into a multi-enzyme complex known as the RNA degradosome. While RNase E forms a homotetramer and PNPase a homotrimer, it remains unclear how these two enzymes interact within the RNA degradosome to potentially satisfy all mutual recognition sites. In this study, we used cryo-EM, biochemistry, and biophysical studies to discover and characterize a new binding mode for PNPase encompassing two or more motifs that are necessary and sufficient for strong interaction with RNase E. While a similar interaction is seen in Salmonella enterica, a different recognition mode arose for Pseudomonas aeruginosa, illustrating the evolutionary drive to maintain physical association of the two ribonucleases. The data presented here suggest a model for the quaternary organization of the RNA degradosome of E. coli, where one PNPase trimer interacts with one RNase E protomer. Conformational transitions are predicted to facilitate substrate capture and transfer to catalytic centres. The model suggests how the endo- and exo-ribonucleases might cooperate in cellular RNA turnover and recruitment of regulatory RNA by the degradosome assembly.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 18","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206933","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

Base-resolution profiling of 5-glyceryl-methylcytosine in Chlamydomonas reinhardtii via deaminase-assisted sequencing. 通过脱氨酶辅助测序对莱茵衣藻中5-甘油甲基胞嘧啶的碱基分辨率分析。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf955

Fan-Chen Wang,Bao-Dan He,Zi-Xin Wang,Xuan Deng,Hui Chen,Wei-Ying Meng,Yu-Tao Fu,Wan-Yue Zou,Tong Ge,Yawen Li,Shu-Xia Sun,Ke-Yao Zhao,Hao-Ming Jiang,Zhi-Yan Sun,Guo-Liang Xu,Kai-Yao Huang,Jian-Huang Xue

{"title":"Base-resolution profiling of 5-glyceryl-methylcytosine in Chlamydomonas reinhardtii via deaminase-assisted sequencing.","authors":"Fan-Chen Wang,Bao-Dan He,Zi-Xin Wang,Xuan Deng,Hui Chen,Wei-Ying Meng,Yu-Tao Fu,Wan-Yue Zou,Tong Ge,Yawen Li,Shu-Xia Sun,Ke-Yao Zhao,Hao-Ming Jiang,Zhi-Yan Sun,Guo-Liang Xu,Kai-Yao Huang,Jian-Huang Xue","doi":"10.1093/nar/gkaf955","DOIUrl":"https://doi.org/10.1093/nar/gkaf955","url":null,"abstract":"5gmC (5-glyceryl-methylcytosine), a vitamin C-derived hypermodified base, has been identified in the genome of Chlamydomonas reinhardtii. However, the global distribution of 5gmC and its role as an epigenetic mark remain poorly understood. In this study, we employed a DNA deaminase to distinguish 5gmC from 5mC (5-methylcytosine) and cytosines, enabling precise profiling of 5gmC across the genome. This deaminase-assisted sequencing demonstrates superior performance compared to the previously proposed TET-coupled bisulfite sequencing. Using both methods, we identified numerous confident 5gmC sites. Unlike 5mC, which predominantly occurs at CpG sites, 5gmC is preferentially located in CHH contexts. Remarkably, over half of 5gmC sites are mutually exclusive from 5mC, with the remaining sites inversely correlated with 5mC levels, suggesting a role in active DNA demethylation. Additionally, 5gmC is enriched within introns, contrasting with the more extensive localization of 5mC in intergenic and promoter regions. Importantly, 5gmC levels are positively correlated with transcription, while 5mC typically exhibits an inverse relationship with gene expression, consistent with the enrichment of 5mC but lack of enrichment of 5gmC at H3K9me1-marked repressive chromatin. Collectively, these findings suggest that 5gmC is not only an intermediate for active DNA demethylation but also functions as a stable epigenetic mark, potentially influencing transcriptional regulation independently of 5mC.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"41 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127152","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

Editor's Note on 'Mutagenesis of human DNA polymerase λ: essential roles of Tyr505 and Phe506 for both DNA polymerase and terminal transferase activities'. 编者注：《人类DNA聚合酶λ的突变：Tyr505和Phe506对DNA聚合酶和末端转移酶活性的重要作用》。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf1017

引用次数: 0

High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS. 高效同源定向插入基因组使用工程归巢内切酶ARCUS。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf961

Laura Christian Resly, Alan L Tubbs, Alexander J Vogel, Jo Ann Hux, Ian A MacDonald, Jason Harris, Adam Mischler, Ginger H Tomberlin, Kathryn S Evans, Rhese Thompson, Jeffrey Sunman, Janel Lape, J Jeff Smith, Aaron J Martin

{"title":"High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS.","authors":"Laura Christian Resly, Alan L Tubbs, Alexander J Vogel, Jo Ann Hux, Ian A MacDonald, Jason Harris, Adam Mischler, Ginger H Tomberlin, Kathryn S Evans, Rhese Thompson, Jeffrey Sunman, Janel Lape, J Jeff Smith, Aaron J Martin","doi":"10.1093/nar/gkaf961","DOIUrl":"10.1093/nar/gkaf961","url":null,"abstract":"Several gene editing tools have entered the clinic, representing varied options for eliminating or correcting mutations. Although gene editing by homologous recombination (HR) can potentially accomplish any type of gene edit (insertions, deletions, and replacements), as the outcome is defined by a recombinant repair template, gene editing enzymes that support efficient HR are rare. ARCUS nucleases, engineered from the homing endonuclease I-CreI, have programmable sequence specificity and support precise, high-frequency transgene insertion. In this study, we demonstrate that the 3' overhangs that ARCUS nucleases generate when cutting DNA are key to triggering high rates of HR. We show that a single editor can be used to accomplish the full range of currently understood DNA editing approaches, allowing all combinations of single base changes, introducing small, specific deletions, small and large insertions, and the ability to replace large segments of genomic DNA with efficiencies ranging from 60% to 90% in lymphocytes. ARCUS also supports precise, efficient insertion (30%-40%) in noncycling hepatocytes via nonclassical HR pathways. Collectively, this work characterizes a flexible and efficient gene insertion system for potential therapeutic use.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 18","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233167","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

Molecular interplay between ComEC domains allows for selective degradation of the non-translocating strand during natural transformation. ComEC结构域之间的分子相互作用允许在自然转化过程中选择性地降解非易位链。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf932

Matthew J M Stedman,Sophie Deselaers,Sebastian A G Braus,Dianhong Wang,Maria Gregori Balaguer,Alvar D Gossert,Manuela K Hospenthal

{"title":"Molecular interplay between ComEC domains allows for selective degradation of the non-translocating strand during natural transformation.","authors":"Matthew J M Stedman,Sophie Deselaers,Sebastian A G Braus,Dianhong Wang,Maria Gregori Balaguer,Alvar D Gossert,Manuela K Hospenthal","doi":"10.1093/nar/gkaf932","DOIUrl":"https://doi.org/10.1093/nar/gkaf932","url":null,"abstract":"Naturally competent bacteria can take up and incorporate environmental DNA using complex machinery in a process called natural transformation. This is a key mechanism in the spread of antibiotic resistance amongst bacteria, including many human pathogens. All competent bacteria require ComEC to transport the transforming DNA across the cytoplasmic membrane. In addition to the transmembrane domain predicted to form the DNA channel, most ComEC orthologues contain an oligonucleotide binding (OB) fold and β-lactamase-like domain. Here, we provide high-resolution structures and an in-depth characterization of the nuclease activity of the β-lactamase-like domain and the DNA-binding activity of the OB fold. We show that the in vitro nuclease activity of the β-lactamase-like domain is enhanced when the OB fold is encoded on the same polypeptide chain. Additionally, we identify a loop within the β-lactamase-like domain, positioned at the entrance of the DNA channel where the duplex DNA separates. Residues in this loop likely guide the non-translocating strand towards the nuclease domain, while a DNA channel lined with aromatic residues provides a path for the translocating strand. On the basis of our biochemical, structural, and functional characterization, we provide a model for how ComEC achieves DNA binding, degradation, and translocation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"40 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116630","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

Dam-dependent epigenetic memory regulates prophage reintegration in Salmonella. 大坝依赖的表观遗传记忆调节沙门氏菌的噬菌体整合。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf951

Jihye Yang,Yongjun Son,Jinwon Park,Woojun Park

{"title":"Dam-dependent epigenetic memory regulates prophage reintegration in Salmonella.","authors":"Jihye Yang,Yongjun Son,Jinwon Park,Woojun Park","doi":"10.1093/nar/gkaf951","DOIUrl":"https://doi.org/10.1093/nar/gkaf951","url":null,"abstract":"Bacterial epigenetics has emerged as a critical mechanism for regulating gene expression in response to environmental cues, yet whether such modifications persist beyond initial stress remains unresolved. Here, we uncover an epigenetic memory system in Salmonella enterica that facilitates prophage reintegration during infection. Using an in vitro model mimicking stages of the Salmonella infection cycle, including the Salmonella-containing vacuole (SCV), we found that DNA adenine methyltransferase (Dam) plays stage-specific roles in adaptation and survival of Salmonella cells. Early during SCV-like stress, oxidative stress contributes to excision of the cryptic prophage ST64B. However, at later infection stages, levels of excised phage DNA decline as global methylation increases, notably at the promoter of intA, a prophage integrase encoded by Salmonella. This methylation persists after stress removal and maintains active intA transcription, establishing a form of epigenetic memory. Functional assays revealed that intA expression is required for efficient ST64B reintegration and that this process depends on methylation at a critical GATC site within the promoter. Mechanistically, we show that SCV stress disrupts binding of the integration host factor, a repressor of intA, thereby enabling Dam-mediated methylation. Sustained intA activation stabilizes prophage reintegration, highlighting stress-responsive epigenetic control important for adaptation during Salmonella pathogenesis.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"89 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116676","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

Residues in the little finger domain of the Y-family Dpo4 DNA polymerase communicate to restrict synthesis past 8-oxoguanine lesions. y家族Dpo4 DNA聚合酶小指结构域的残基相互交流，限制8-氧鸟嘌呤损伤后的合成。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf950

Sadia Sinty Disha,Thushani I Punchipatabendi,Joseph D Kaszubowski,Biqing Liang,Janice D Pata,Michael A Trakselis

{"title":"Residues in the little finger domain of the Y-family Dpo4 DNA polymerase communicate to restrict synthesis past 8-oxoguanine lesions.","authors":"Sadia Sinty Disha,Thushani I Punchipatabendi,Joseph D Kaszubowski,Biqing Liang,Janice D Pata,Michael A Trakselis","doi":"10.1093/nar/gkaf950","DOIUrl":"https://doi.org/10.1093/nar/gkaf950","url":null,"abstract":"Endogenous reactive oxygen species are responsible for abundant 8-oxo-7,8-dihydroguanine (8-oxoG) lesion formation in all three domains of life. In the archaeal Saccharolobus solfataricus(Sso), a specialized translesion synthesis (TLS) polymerase, SsoDpo4, is recruited to bypass lesions when the high-fidelity polymerase stalls. Previous studies have found that SsoDpo4 can accurately bypass 8-oxoG lesions with deoxycytosine and then efficiently extend three nucleotides beyond the lesion to the +3 position. Here, we have mutated several arginines within the little finger (LF) domain that track along the phosphate backbone near the active site and tested their extension ability and DNA binding properties. Mutation of two key residues, R332 or R336, to alanine relieves +3 intermediate accumulation, resulting in more efficient full-length extension. Interestingly, the wild-type enzyme binds progressively weaker downstream of a bypassed 8-oxoG lesion, indicating decreased binding stability after lesion bypass. X-ray crystallography has captured these mutants on the +3 extended primer/8-oxoG template to structurally characterize how these LF residues communicate to restrict downstream synthesis past 8-oxoG. Our results offer mechanistic and structural insights into how TLS polymerases restrict downstream synthesis past a lesion by sensing backbone distortions and altering domain conformations to limit catalysis and destabilize binding.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"18 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140443","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

Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs. 修饰的未锁定核酸（MUNA）减轻了小干扰rna的脱靶效应。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf937

Shohei Mori,Dhrubajyoti Datta,Lydia Perkins,Michelle Jung,Lauren Blair Woods,Alex Eaton,June Qin,Tim Racie,MaryBeth Kim,Dale C Guenther,Adam Castoreno,Mark K Schlegel,Klaus Charisse,Martin Egli,Shigeo Matsuda,Muthiah Manoharan

{"title":"Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.","authors":"Shohei Mori,Dhrubajyoti Datta,Lydia Perkins,Michelle Jung,Lauren Blair Woods,Alex Eaton,June Qin,Tim Racie,MaryBeth Kim,Dale C Guenther,Adam Castoreno,Mark K Schlegel,Klaus Charisse,Martin Egli,Shigeo Matsuda,Muthiah Manoharan","doi":"10.1093/nar/gkaf937","DOIUrl":"https://doi.org/10.1093/nar/gkaf937","url":null,"abstract":"Unlocked nucleic acid (UNA) is a nucleic acid analog that has an acyclic ribose ring lacking the bond between C2' and C3' atoms. The base-pairing properties of UNA have been studied, and it has been used as a scaffold for conjugation, but the chemical space around UNA and its potential applications in the context of short interfering RNAs (siRNAs), which mediate RNA interference, have not been thoroughly explored. In this study, we report syntheses of methylated and methoxylated UNAs and their incorporation into siRNAs. siRNAs with 5'-(R)-methyl-UNA and with 5'-(S)-methyl-UNA in the seed region had comparable potencies but reduced off-target effects compared to siRNA modified with UNA. In mice, siRNAs with modified UNAs were of comparable potency to an siRNA of the same sequence and chemistry lacking UNA. Modeling studies indicated that the flexibilities of UNA and the modified UNAs facilitate kinking of the antisense strand when incorporated at position 7. These findings highlight the potential of modified UNA for advancing therapeutics that act through the RNA interference pathway.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"21 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182728","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

Angel wing: a class of alternative splicing regulators in animals. 天使翼：动物中一类可选择的剪接调节器。

IF 13.1 2区生物学

Nucleic Acids Research Pub Date : 2025-09-23 DOI: 10.1093/nar/gkaf972

Ting Zhang, Kaili Li, Ying Xiao, Xiaoyan Tan, Xionghong Tan, Min Cui, Yikang S Rong

{"title":"Angel wing: a class of alternative splicing regulators in animals.","authors":"Ting Zhang, Kaili Li, Ying Xiao, Xiaoyan Tan, Xionghong Tan, Min Cui, Yikang S Rong","doi":"10.1093/nar/gkaf972","DOIUrl":"10.1093/nar/gkaf972","url":null,"abstract":"Alternative splicing (AS) regulates the diversity and level of the proteome. The specificity in AS is in turn regulated by RNA-binding proteins, but our understanding of how they act is far from complete. Here, we identify the Angel wing (Anw) protein, previously CG10948, as a novel AS regulator. Loss of Anw in Drosophila disrupts splicing in muscle genes and subsequently muscle function. Based on a mini-gene assay in which Anw and its RNA targets are co-expressed in cultured cells, we demonstrated orthologous splicing regulation of the mini-gene transcripts, interaction between Anw and its RNA targets, and a remarkable functional conservation among Anw homologs. Anw forms nuclear foci, and genetic ablation of Anw domains suggests that maintaining distinctive features of these foci is important for its function. The evolution of Anw is dynamic with gene gains and losses, but as others suggested, preserves a cross-phyla \"ultra conserved element\" as an alternative exon that potentially regulates its own level by nonsense-mediated mRNA decay. As the human anw homolog is a candidate gene for myasthenia gravis, our work suggests a mechanism for cellular dysfunction in this disease.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 18","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150283","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