Communications Biology最新文献_第9页

The Vulpes vulpes montana genome provides insights into high-altitude adaptation mechanisms of the Vulpes species. 蒙大拿Vulpes Vulpes基因组为Vulpes物种的高海拔适应机制提供了见解。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-18 DOI: 10.1038/s42003-025-08450-9

Tianshu Lyu, Zhao Liu, Tian Xia, Shengyang Zhou, Jiaohui Fang, Kaijia Dong, Lidong Wang, Lupeng Shi, Yuehuan Dong, Zihao Sheng, Xiaoyang Wu, Xiufeng Yang, Honghai Zhang

{"title":"The Vulpes vulpes montana genome provides insights into high-altitude adaptation mechanisms of the Vulpes species.","authors":"Tianshu Lyu, Zhao Liu, Tian Xia, Shengyang Zhou, Jiaohui Fang, Kaijia Dong, Lidong Wang, Lupeng Shi, Yuehuan Dong, Zihao Sheng, Xiaoyang Wu, Xiufeng Yang, Honghai Zhang","doi":"10.1038/s42003-025-08450-9","DOIUrl":"10.1038/s42003-025-08450-9","url":null,"abstract":"Vulpes vulpes montana (V. v. montana) and Vulpes ferrilata (V. ferrilata) are the only two Vulpes species known to inhabit the Qinghai-Xizang Plateau. Exploring the high-altitude (HA) adaptation mechanisms in Vulpes species may broaden our understanding of the genetic adaptability of species to HA environments. In this study, we constructed a high-quality chromosome-level genome for V. v. montana. The assembled genome was ~2.34 Gb and N50 length of 139.03 Mb, and 99.51% (~2.33 Gb) of the assembly was anchored into 17 pseudo-chromosomes. A total of 20,056 protein-coding genes were predicted in the assembled genome, 93.06% of which were functionally annotated. Comparative genomics analysis reveals unique and shared HA adaptation mechanisms in HA Vulpes species. Further, we identified a parallel amino acid site substitution (Serine to Phenylalanine) at position 132 in the IGSF22 gene that is present in HA Vulpes species. This mutation significantly enhances the expression of this immune-related gene under hypoxic conditions and also markedly up-regulates the expression of genes associated with angiogenesis (AKT1, ABCG2 and VEGFA). Our study reveals the molecular mechanism of HA adaptation in Vulpes species and provides a high-quality genomic resource for future research.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1070"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Assisting and accelerating NMR assignment with restrained structure prediction. 用约束结构预测辅助和加速核磁共振分配。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-18 DOI: 10.1038/s42003-025-08466-1

Sirui Liu, Haotian Chu, Yuhao Xie, Fangming Wu, Fangjing Mu, Jiachen Wei, Ningxi Ni, Chenghao Wang, Jun Zhang, Mengyun Chen, Junbin Li, Fan Yu, Hui Fu, Shenlin Wang, Changlin Tian, Zidong Wang, Yi Qin Gao

{"title":"Assisting and accelerating NMR assignment with restrained structure prediction.","authors":"Sirui Liu, Haotian Chu, Yuhao Xie, Fangming Wu, Fangjing Mu, Jiachen Wei, Ningxi Ni, Chenghao Wang, Jun Zhang, Mengyun Chen, Junbin Li, Fan Yu, Hui Fu, Shenlin Wang, Changlin Tian, Zidong Wang, Yi Qin Gao","doi":"10.1038/s42003-025-08466-1","DOIUrl":"10.1038/s42003-025-08466-1","url":null,"abstract":"Accurate dynamic protein structures are essential for drug design. NMR experiments can detect protein structures and potential dynamics, but the spectrum assignment and structure determination requires expertise and is time-consuming, while deep-learning-based structure predictions may be inconsistent with experimental observations. A symbiosis between experiments and AI methods is therefore essential for solving such problems. Here, we developed a Restraint Assisted Structure Predictor (RASP) model and an iterative Folding Assisted peak ASsignmenT (FAAST) pipeline directly leveraging experimental information to improve the AI-assisted structure prediction and facilitate experimental data analysis in an integrative way. The RASP model improves structure prediction, especially for multi-domain and few-MSA proteins. The FAAST pipeline for NMR NOESY analysis reduces the time consumption to hours and yields high quality structure ensemble. Both methods show high consistency between predicted structures and restraints, provided or iteratively assigned. This strategy can be expanded to other types of sparse experimental information in structure prediction.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1067"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

An inner membrane protein is covalently attached to peptidoglycan in the γ-proteobacterium Dickeya dadantii. γ-变形杆菌中的一种内膜蛋白与肽聚糖共价结合。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-18 DOI: 10.1038/s42003-025-08488-9

Xavier Nicolai, Yucheng Liang, Florence Ruaudel, Magdalena Narajczyk, Robert Czajkowski, Filippo Rusconi, Michel Arthur, Vladimir E Shevchik

{"title":"An inner membrane protein is covalently attached to peptidoglycan in the γ-proteobacterium Dickeya dadantii.","authors":"Xavier Nicolai, Yucheng Liang, Florence Ruaudel, Magdalena Narajczyk, Robert Czajkowski, Filippo Rusconi, Michel Arthur, Vladimir E Shevchik","doi":"10.1038/s42003-025-08488-9","DOIUrl":"10.1038/s42003-025-08488-9","url":null,"abstract":"Gram-negative (diderm) bacteria possess a multilayered envelope comprising an inner membrane, a thin peptidoglycan (PG) layer and an outer membrane. In Escherichia coli and certain other γ-proteobacteria, including Dickeya dadantii, Braun lipoprotein, Lpp, covalently tethers the outer membrane to PG. Here, we show that in D. dadantii an inner membrane protein, OutB, is covalently attached to PG by the same catalytic mechanism as Lpp. Specifically, two L,D-transpeptidases, Ldt03 and Ldt84, catalyze protein attachment with a preference for muropeptide monomers and dimers, respectively. By altering the Lpp length, we show that the extended Lpp+21 enhances OutB attachment to PG, whereas the truncated LppΔ21 reduces it. Furthermore, we show that the PG-anchoring sequence of OutB tolerates substantial amino acid substitutions and allows PG-tethering of a periplasmic reporter protein, suggesting that other periplasmic and/or membrane proteins may also be tethered to PG in proteobacteria.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1071"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Bivalent single-domain antibodies show potent mpox virus neutralization through M1R antigen. 双价单域抗体通过M1R抗原表现出有效的m痘病毒中和作用。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-18 DOI: 10.1038/s42003-025-08494-x

Daisuke Akazawa, Masayuki Shimojima, Eun-Sil Park, Akiko Okutani, Milagros Virhuez-Mendoza, Yusuke Inoue, Takayuki Hishiki, Ken Maeda, Hideki Ebihara, Yoshimasa Takahashi, Koichi Watashi

{"title":"Bivalent single-domain antibodies show potent mpox virus neutralization through M1R antigen.","authors":"Daisuke Akazawa, Masayuki Shimojima, Eun-Sil Park, Akiko Okutani, Milagros Virhuez-Mendoza, Yusuke Inoue, Takayuki Hishiki, Ken Maeda, Hideki Ebihara, Yoshimasa Takahashi, Koichi Watashi","doi":"10.1038/s42003-025-08494-x","DOIUrl":"10.1038/s42003-025-08494-x","url":null,"abstract":"Despite the recent mpox outbreak raising global concerns, no fully validated antiviral treatment exists, highlighting the urgent need for effective therapeutics. Here, by taking advantage of the preparation technology for single-domain (VHH) antibodies, we generated VHHs targeting the six major mpox virus (MPXV) surface antigens. Although neutralization activity of these monoclonal VHH monomers was negligible, bivalent VHHs against MPXV-M1R (bi-M1A8 and bi-M1C2) improved the antigen binding affinity by up to over 400-fold compared with the monomer VHH and thus produced neutralizing activity against MPXV. Epitope analysis by SPR revealed that the two neutralizing bivalent VHHs recognized different epitopes within M1R antigen. Importantly, these bivalent VHHs were active to multiple MPXV clades and related cowpox virus. We also showed the effect of bi-M1A8 on reducing the MPXV DNA and infectious titer in an MPXV infection mouse model. These VHH modification approaches provide a new strategy for anti-MPXV drug development.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1073"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Reduced maternal SCFAs in GDM diminish GPR43 signaling and induce offspring CAKUT. GDM中母体SCFAs减少，GPR43信号减少，诱导子代CAKUT。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-17 DOI: 10.1038/s42003-025-08469-y

He Wang, Tianyang Kang, Weiwei Li

引用次数: 0

Abnormal development of gastrointestinal system of homozygous Foxp2(R552H)-mutated mice. 纯合子Foxp2（R552H）突变小鼠胃肠道系统发育异常。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-17 DOI: 10.1038/s42003-025-08468-z

Eriko Fujita-Jimbo, Sachie Nakamura, Katsuko Sudo, Takashi Momoi

{"title":"Abnormal development of gastrointestinal system of homozygous Foxp2(R552H)-mutated mice.","authors":"Eriko Fujita-Jimbo, Sachie Nakamura, Katsuko Sudo, Takashi Momoi","doi":"10.1038/s42003-025-08468-z","DOIUrl":"10.1038/s42003-025-08468-z","url":null,"abstract":"Forkhead box protein P2 (Foxp2) regulates the expression of genes related to organ morphogenesis. Homozygous Foxp2(R552H) knock-in (Foxp2R552H/R552H) mice exhibit abnormal brain development, and die around the weaning period. Here we demonstrate that Foxp2R552H/R552H mice exhibit abnormal development of gastrointestinal (GI) system, followed by atrophy of stomach, abnormal rotation of intestine, and decreased expression of genes related to GI system development such as bar-like home box 1 (BARX1) and secreted frizzled-related protein 1 (Sfrp1), antagonist for Wnt/β-catenin signaling, and decreased expression of E-cadherin and Zonula occludens-1 (ZO-1) in epithelium, followed with increase of Zonulin in the serum, marker of leaky gut, and decrease of alpha-smooth muscle actin (SMA) in smooth muscle, resulting in their atrophy. Foxp2+/+ and Foxp2R552H/R552H transgenic mice expressing Foxp2 promoter-mediated mCherry exhibit that Foxp2 autoregulates its expression in the developing stomach. Foxp2 may control Wnt/β-catenin signaling via its autoregulation system, but Foxp2(R552H) may not. Our results suggest that Foxp2 is necessary for the development of the GI system.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1059"},"PeriodicalIF":5.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Affective information modulates slow-wave- and arousal-like responses during NREM sleep. 情感信息调节非快速眼动睡眠期间的慢波和唤醒样反应。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-17 DOI: 10.1038/s42003-025-08480-3

Demetrio Grollero, Damiana Bergamo, Alessandra Federici, Ruggero Basanisi, Davide Bottari, Monica Betta, Giulio Bernardi

{"title":"Affective information modulates slow-wave- and arousal-like responses during NREM sleep.","authors":"Demetrio Grollero, Damiana Bergamo, Alessandra Federici, Ruggero Basanisi, Davide Bottari, Monica Betta, Giulio Bernardi","doi":"10.1038/s42003-025-08480-3","DOIUrl":"10.1038/s42003-025-08480-3","url":null,"abstract":"Sleep is characterized by relative disconnection from the external environment and prompt reversibility in response to salient stimuli. During non-rapid eye movement (NREM) sleep, reactive electroencephalographic (EEG) slow waves (K-complexes, KC) are thought to both suppress the processing of external stimuli and open 'sentinel' windows during which further relevant inputs may be tracked. However, the extent to which a stimulus's relevance modulates the KC-related response remains unclear. Here, we investigated the impact of emotional information in human vocal bursts on KC and post-KC activity. Twenty-five young adults were presented with vocal bursts conveying negative, neutral, and positive emotions. We found that affective content influenced the rate, amplitude, and cortical distribution of KCs, as well as post-KC high-frequency activity. These results indicate that KCs are not all-or-none responses and that salient information is not entirely 'quenched' by KCs. These insights offer new perspectives on how sleep continuity and reversibility are regulated.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1060"},"PeriodicalIF":5.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CÓDIGO): building local capacity in genomics and bioinformatics. 哥伦比亚基因组多样性、祖先和健康联合会（CÓDIGO）：建设基因组学和生物信息学方面的地方能力。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-17 DOI: 10.1038/s42003-025-08496-9

Leonardo Mariño-Ramírez, Shivam Sharma, James Matthew Hamilton, Thanh Long Nguyen, Sonali Gupta, Aravinth Venkatesh Natarajan, Shashwat Deepali Nagar, Jay Landon Menuey, Wei-An Chen, Adalberto Sánchez-Gómez, José María Satizábal-Soto, Beatriz Martínez, Javier Marrugo, Miguel A Medina-Rivas, Juan Esteban Gallo, I King Jordan, Augusto Valderrama-Aguirre

{"title":"The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CÓDIGO): building local capacity in genomics and bioinformatics.","authors":"Leonardo Mariño-Ramírez, Shivam Sharma, James Matthew Hamilton, Thanh Long Nguyen, Sonali Gupta, Aravinth Venkatesh Natarajan, Shashwat Deepali Nagar, Jay Landon Menuey, Wei-An Chen, Adalberto Sánchez-Gómez, José María Satizábal-Soto, Beatriz Martínez, Javier Marrugo, Miguel A Medina-Rivas, Juan Esteban Gallo, I King Jordan, Augusto Valderrama-Aguirre","doi":"10.1038/s42003-025-08496-9","DOIUrl":"10.1038/s42003-025-08496-9","url":null,"abstract":"The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CÓDIGO) aims to build a community of Colombian researchers in support of local capacity in genomics, bioinformatics, and precision health. Here, we present the first CÓDIGO data release and the consortium web platform, including annotations for more than 95 million genetic variants from 1441 samples representing 14 populations from across the country. CÓDIGO samples show a wide range of African (16.7%), Indigenous American (32.8%), and European (50.6%) genetic ancestry components, with five distinct ancestry clusters. Thousands of ancestry-enriched variants, with divergent allele frequencies across clusters, show pharmacogenomic and clinical genetic associations. Examples include African ancestry-enriched variants associated with fast metabolism of the immunosuppressive drug tacrolimus and malaria resistance, and European ancestry-enriched variants associated with nicotine dependence and hereditary hemochromatosis. CÓDIGO reveals the nexus between ancestry and health in Colombia and underscores the utility of collaborative genome sequence analysis efforts.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1062"},"PeriodicalIF":5.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Characterization of an unusual SARS-CoV-2 main protease natural variant exhibiting resistance to nirmatrelvir and ensitrelvir. 一种不寻常的SARS-CoV-2主要蛋白酶天然变体的特征，表现出对尼马特瑞韦和恩西瑞韦的抗性。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-17 DOI: 10.1038/s42003-025-08487-w

Dipendra Bhandari, Oksana Gerlits, Stephen Keable, Leighton Coates, Annie Aniana, Rodolfo Ghirlando, Nashaat T Nashed, Andrey Kovalevsky, John M Louis

{"title":"Characterization of an unusual SARS-CoV-2 main protease natural variant exhibiting resistance to nirmatrelvir and ensitrelvir.","authors":"Dipendra Bhandari, Oksana Gerlits, Stephen Keable, Leighton Coates, Annie Aniana, Rodolfo Ghirlando, Nashaat T Nashed, Andrey Kovalevsky, John M Louis","doi":"10.1038/s42003-025-08487-w","DOIUrl":"10.1038/s42003-025-08487-w","url":null,"abstract":"We investigate the effects of two naturally selected substitution and deletion (Δ) mutations, constituting part of the substrate binding subsites S2 and S4, on the structure, function, and inhibition of SARS CoV-2 main protease. Comparable to wild-type, MProD48Y/ΔP168 undergoes N-terminal autoprocessing essential for stable dimer formation and mature-like catalytic activity. The structures are similar, but for an open active site conformation in MProD48Y/ΔP168 and increased dynamics of the S2 helix, S5 loop, and the helical domain. Some dimer interface contacts exhibit shorter H bond distances corroborating the ~40-fold enhanced dimerization of the mutant although its thermal sensitivity to unfolding is 8 °C lower, relative to wild-type. ITC reveals a 3- and 5-fold decrease in binding affinity for nirmatrelvir and ensitrelvir, respectively, and similar GC373 affinity, to MProD48Y/ΔP168 relative to wild-type. Structural differences in four inhibitor complexes of MProD48Y/ΔP168 compared to wild-type are described. Consistent with enhanced dynamics, the S2 helix and S5 loop adopting a more open conformation appears to be a unique feature of MProD48Y/ΔP168 both in the inhibitor-free and bound states. Our results suggest that mutational effects are compensated by changes in the conformational dynamics and thereby modulate N-terminal autoprocessing, Kdimer, catalytic efficiency, and inhibitor binding.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1061"},"PeriodicalIF":5.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Long-read RNA sequencing unveils a novel cryptic exon in MNAT1 along with its full-length transcript structure in TDP-43 proteinopathy. 长读RNA测序揭示了TDP-43蛋白病中MNAT1的一个新的隐外显子及其全长转录本结构。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-07-16 DOI: 10.1038/s42003-025-08463-4

Yoshihisa Tanaka, Naohiro Sunamura, Rei Kajitani, Marie Ikeguchi, Ryo Kunimoto

{"title":"Long-read RNA sequencing unveils a novel cryptic exon in MNAT1 along with its full-length transcript structure in TDP-43 proteinopathy.","authors":"Yoshihisa Tanaka, Naohiro Sunamura, Rei Kajitani, Marie Ikeguchi, Ryo Kunimoto","doi":"10.1038/s42003-025-08463-4","DOIUrl":"10.1038/s42003-025-08463-4","url":null,"abstract":"Understanding the role of transcript isoforms is essential for elucidating disease mechanisms. TDP-43 regulates RNA splicing, and its dysfunction in neurons is a hallmark of some neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). While an association between TDP-43-dependent cryptic exons and disease pathogenesis has been suggested, an approach to investigate how cryptic exons disrupt transcript isoforms has yet to be established. In this study, we developed IsoRefiner, a novel method for identifying full-length transcript structures using long-read RNA-seq. Leveraging this method, we performed long-read RNA-seq, guided by prior short-read RNA-seq, to comprehensively determine the full-length structures of aberrant transcripts due to TDP-43 dysregulation in human iPSC-derived motor neurons. We identified a novel TDP-43-dependent cryptic exon in the MNAT1 gene, along with its full-length transcript structure. Furthermore, we confirmed the presence of the MNAT1 cryptic exon in patients with ALS and FTD. Our findings deepen understanding of TDP-43 proteinopathy and advance splicing research.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1056"},"PeriodicalIF":5.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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