Molecular and Cellular Biology最新文献_第4页

Enhanced ELL Phase Separation Is Crucial for Efficient DNA Damage Repair to Restart Transcription and Cell Survival. 增强的ELL相分离对于有效的DNA损伤修复、重启转录和细胞存活至关重要。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-22 DOI: 10.1080/10985549.2025.2597497

Sujay Pal, Prathama Talukdar, Arijit Ghosh, Sangheeta Bhattacharjee, Sumangal Roychowdhury, Pamela Pal, Anupam Gautam, Subham Basu, Sandip Paul, Krishnananda Chattopadhyay, Benu Brata Das, Debabrata Biswas

{"title":"Enhanced ELL Phase Separation Is Crucial for Efficient DNA Damage Repair to Restart Transcription and Cell Survival.","authors":"Sujay Pal, Prathama Talukdar, Arijit Ghosh, Sangheeta Bhattacharjee, Sumangal Roychowdhury, Pamela Pal, Anupam Gautam, Subham Basu, Sandip Paul, Krishnananda Chattopadhyay, Benu Brata Das, Debabrata Biswas","doi":"10.1080/10985549.2025.2597497","DOIUrl":"10.1080/10985549.2025.2597497","url":null,"abstract":"During genotoxic stress, mammalian cells adapt to resume transcription after repair of damaged DNA. However, mechanisms of these adaptations leading to optimal transcriptional restart are poorly known. In this study, we show critical role of EAF1-mediated enhanced phase separation of elongation factor ELL in its interaction with DNA repair factors for efficient repair of damaged DNA and subsequent transcriptional restart. ELL protein has intrinsic ability to phase separate and form liquid condensates both in vitro and in vivo within mammalian cells. Upon association with EAF1, intrinsic phase separation ability of ELL is enhanced resulting in changes in material property of ELL●EAF1 condensates. Physiologically, upon exposure to genotoxic stress, ATM-mediated phosphorylation-dependent increased EAF1 binding leads to enhanced phase separation and changes the material property of ELL. This, in turn, causes its increased interaction with DNA-PKc and associated Ku complex components. This increased interaction is important for their optimal recruitment on chromatin and corresponding repair of damaged DNA and transcriptional restart. An EAF1 knockdown or ELL mutant that fails to show its enhanced interaction with EAF1 during DNA damage, also fails to show efficient DNA damage repair, transcriptional restart and cell survival after exposure to genotoxic stress.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"209-237"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804877","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

Targeting Ubiquitinated Protein Aggregates in Neurodegenerative Diseases: current Status and Future Directions. 靶向泛素化蛋白聚集体治疗神经退行性疾病：现状与未来方向

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-08-04 DOI: 10.1080/10985549.2026.2705871

Masahiko Takahashi, Takayuki Abe, Masahiro Fujii

{"title":"Targeting Ubiquitinated Protein Aggregates in Neurodegenerative Diseases: current Status and Future Directions.","authors":"Masahiko Takahashi, Takayuki Abe, Masahiro Fujii","doi":"10.1080/10985549.2026.2705871","DOIUrl":"10.1080/10985549.2026.2705871","url":null,"abstract":"Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism in neurodegenerative proteinopathies, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). TAR DNA-binding protein 43 (TDP-43) and Tau are causative factors in ALS and AD, respectively, and both localize to SGs under stress conditions. During disease progression, TDP-43 or Tau within SGs undergoes pathological changes that promote the formation of neurotoxic inclusions, which propagate neuronal dysfunction and death. This review summarizes recent advances in understanding the molecular factors that regulate SG assembly and disassembly, as well as the pathological processes that drive the conversion of SGs into aggregates associated with neurodegenerative diseases. Particular emphasis is placed on the role of the ubiquitin-specific protease 10 (USP10), which modulates SG dynamics and has been mechanistically implicated in both ALS and AD. Finally, we discuss the therapeutic potential of targeting these pathways to mitigate neurodegenerative disease progression.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1035-1053"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670212","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

Loss of Splicing Homeostasis as a Hallmark of Aging. 剪接稳态丧失是衰老的标志。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-03-02 DOI: 10.1080/10985549.2026.2627235

Stefano Donega, Myriam Gorospe, Lorna W Harries, Luigi Ferrucci

{"title":"Loss of Splicing Homeostasis as a Hallmark of Aging.","authors":"Stefano Donega, Myriam Gorospe, Lorna W Harries, Luigi Ferrucci","doi":"10.1080/10985549.2026.2627235","DOIUrl":"10.1080/10985549.2026.2627235","url":null,"abstract":"Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that \"transcriptomic instability\" is a hallmark of aging.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"673-691"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343635","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

mTORC1-Dependent Regulation of the CCL24-CCR3 Axis Controls Granuloma Formation and Maintenance in Sarcoidosis. mtorc1依赖性调控CCL24-CCR3轴控制结节病肉芽肿的形成和维持。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-06-05 DOI: 10.1080/10985549.2026.2680144

Xiongjian Rao, Jinpeng Liu, Derek B Allison, Douglas A Harrison, Ka Wing Fong, Yuanyuan Wu, Daheng He, Jia Peng, Zhiguo Li, Chi Wang, Jamie L Sturgill, Parijat Sen, Xiaoqi Liu

{"title":"mTORC1-Dependent Regulation of the CCL24-CCR3 Axis Controls Granuloma Formation and Maintenance in Sarcoidosis.","authors":"Xiongjian Rao, Jinpeng Liu, Derek B Allison, Douglas A Harrison, Ka Wing Fong, Yuanyuan Wu, Daheng He, Jia Peng, Zhiguo Li, Chi Wang, Jamie L Sturgill, Parijat Sen, Xiaoqi Liu","doi":"10.1080/10985549.2026.2680144","DOIUrl":"10.1080/10985549.2026.2680144","url":null,"abstract":"Sarcoidosis is a chronic granulomatous disease marked by persistent inflammation and immune cell aggregation, yet its molecular underpinnings remain incompletely understood, hindering the development of effective targeted therapies. Here, we report that deletion of Tsc1 or Tsc2 in mice using a Fsp1-Cre leads to spontaneous formation of sarcoid-like granulomas, driven by hyperactivation of the mTORC1 pathway in fibroblasts and interstitial macrophages. Through inflammatory cytokine/chemokine array, we identified CCL24, a chemokine ligand for CCR3, as a key immunoregulatory molecule downregulated in both our murine model and sarcoid cohort plasma. Mechanistically, mTORC1 suppresses CCL24 expression via aberrant STAT3 signaling in fibroblasts and promotes CCR3 expression in interstitial macrophages, uncovering a novel regulatory axis in granuloma formation and maintenance. Pharmacological inhibition using rapamycin and azithromycin markedly attenuated granuloma burden and normalized CCL24-CCR3 signaling, underscoring the therapeutic relevance of this axis. Together, our study establishes a mechanistic link between mTORC1 activation, CCL24-CCR3 dysregulation, and granuloma persistence, offering not only a new insight into molecular mechanisms in sarcoidosis, but also identifying promising targets for clinical intervention.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"724-745"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163790","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

Hsp70/Hsp90 Organizing Protein (HOP) Maintains CRAF Kinase Activity and Regulates MAPK Signaling by Enhancing Hsp90-CRAF Association. Hsp70/Hsp90组织蛋白（HOP）通过增强Hsp90-CRAF关联维持CRAF激酶活性并调控MAPK信号传导。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-04-14 DOI: 10.1080/10985549.2026.2647809

Nilanjan Gayen, Sahana Mitra, Somesh Roy, Atin K Mandal

{"title":"Hsp70/Hsp90 Organizing Protein (HOP) Maintains CRAF Kinase Activity and Regulates MAPK Signaling by Enhancing Hsp90-CRAF Association.","authors":"Nilanjan Gayen, Sahana Mitra, Somesh Roy, Atin K Mandal","doi":"10.1080/10985549.2026.2647809","DOIUrl":"10.1080/10985549.2026.2647809","url":null,"abstract":"The stability and activity of CRAF/Raf1 kinase are stringently regulated by heat shock protein 90 (Hsp90). Hsp90-mediated client folding and maturation are governed by its co-chaperones, but their functionality in chaperoning CRAF kinase to support signaling under physiological conditions remains poorly understood. Here, we show that Hsp70/Hsp90 organizing protein (HOP) associates with CRAF kinase tomaintain its activity and facilitates MAPK pathway activation. This activation is mediated by TPR2A-2B-DP2 domain of HOP and requires efficient binding to Hsp90. Although Cdc37 recruits Hsp90, it cannot compensate for HOP function. Downregulation of HOP/Sti1 in yeast and mammalian cell culture significantly reduces the CRAF signaling. Our data suggest that Hsp90 is recruited to CRAF in two distinct steps: first during folding/maturation via HOP and Cdc37, and later during activation mediated by HOP. Therefore, HOP is a regulator of CRAF kinase during activation of MAPK pathway and serves as a modulator of growth signaling beyond its client folding and maturation function.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"597-616"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691097","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

From Biogenesis to Breakdown: How Protein Biogenesis and Quality Control Failures Drive Mitochondrial Disease. 从生物发生到分解：蛋白质生物发生和质量控制失败如何驱动线粒体疾病。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-10-17 DOI: 10.1080/10985549.2025.2566671

Phoebe J Leeming, Julia Mercuri-Svik, Diana Stojanovski

{"title":"From Biogenesis to Breakdown: How Protein Biogenesis and Quality Control Failures Drive Mitochondrial Disease.","authors":"Phoebe J Leeming, Julia Mercuri-Svik, Diana Stojanovski","doi":"10.1080/10985549.2025.2566671","DOIUrl":"10.1080/10985549.2025.2566671","url":null,"abstract":"Mitochondria rely on the coordinated function of over 1000 proteins, most of which are nuclear-encoded, synthesized in the cytosol, and imported into distinct mitochondrial sub-compartments. Thirteen additional proteins are synthesized within the organelle itself, forming core components of the oxidative phosphorylation (OXPHOS) system. Once inside, mitochondrial precursors undergo precise maturation, folding, and assembly, supported by specialized factors that ensure their function. These processes are safeguarded by an intricate network of chaperones, proteases, and disaggregases that maintain proteome integrity. Protein biogenesis and quality control are deeply interconnected, operating continuously to preserve mitochondrial function. Disruption at any stage, whether in import, folding, assembly, or degradation, can lead to proteotoxic stress and mitochondrial dysfunction, underlying a wide spectrum of mitochondrial diseases. Despite progress in characterizing many of these pathways in human cells, large gaps in knowledge remain. A complete understanding of protein biogenesis and surveillance mechanisms is essential to uncover how their dysregulation drives disease. This knowledge will be foundational for interpreting pathogenic mutations, predicting disease mechanisms, and ultimately guiding therapeutic strategies aimed at restoring mitochondrial proteostasis and health.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"21-47"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313287","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

Deletion of Adaptor Protein ShcD Impairs Olfactory Bulb Morphology and Function. 接头蛋白ShcD的缺失损害嗅球形态和功能。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-15 DOI: 10.1080/10985549.2025.2567559

Hannah N Robeson, Laura A New, Begüm Alural, Cassandra Clausen, Kelsy S J Ervin, Hyeyun Yang, C James Cooper, Elena Choleris, Jasmin Lalonde, Nina Jones

{"title":"Deletion of Adaptor Protein ShcD Impairs Olfactory Bulb Morphology and Function.","authors":"Hannah N Robeson, Laura A New, Begüm Alural, Cassandra Clausen, Kelsy S J Ervin, Hyeyun Yang, C James Cooper, Elena Choleris, Jasmin Lalonde, Nina Jones","doi":"10.1080/10985549.2025.2567559","DOIUrl":"10.1080/10985549.2025.2567559","url":null,"abstract":"Shc family adaptor proteins are involved in diverse signaling pathways that regulate critical cellular functions, including proliferation, differentiation, migration, and survival. ShcD is the most recently isolated member and while previous studies have identified its prominent expression in the brain, specifically within the olfactory bulb, its physiological functions remain largely unknown. Here we report initial characterization of ShcD knockout (ShcDKO) mice and identify structural, behavioral, and biochemical deficits associated with ShcD deletion. Specifically, ShcDKO mice have decreased olfactory bulb weight with a corresponding reduced granule cell layer compared to controls, and defects in olfactory performance. Intriguingly, ShcDKO mice display increased proliferation in the subventricular zone, which serves as the reservoir for neural progenitors migrating into the olfactory bulb. Supporting these cellular changes, we noted Erk2 hyperactivation in the olfactory bulb of ShcDKO mice, and using a cultured neuron model, we also detected altered signaling of Erk5, a MAPK protein associated with neural stem cell differentiation, as well as increased p66ShcA expression, indicating a potential compensatory mechanism within the Shc family. These results uncover a possible physiological role for ShcD in neurogenesis and imply its involvement in signaling pathways that regulate stem cell maintenance and/or differentiation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"253-269"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757004","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

Dual Sub‑MIC Copper-Gentamicin Stress Drives Strain‑Specific, Non‑Additive Phenotypic Shifts in Pseudomonas aeruginosa. 双亚MIC铜-庆大霉素应激驱动铜绿假单胞菌菌株特异性，非加性表型转移。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-07-07 DOI: 10.1080/10985549.2026.2693283

Agata Dorotkiewicz-Jach, Patrycja Paszkowska, Barbara Maciejewska, Zuzanna Drulis-Kawa

{"title":"Dual Sub‑MIC Copper-Gentamicin Stress Drives Strain‑Specific, Non‑Additive Phenotypic Shifts in Pseudomonas aeruginosa.","authors":"Agata Dorotkiewicz-Jach, Patrycja Paszkowska, Barbara Maciejewska, Zuzanna Drulis-Kawa","doi":"10.1080/10985549.2026.2693283","DOIUrl":"10.1080/10985549.2026.2693283","url":null,"abstract":"Exposure to redox‑active metals and sub‑inhibitory antibiotics represents a significant selective pressure shaping bacterial physiology and antimicrobial susceptibility. Here, we investigated how four genetically and phenotypically distinct Pseudomonas aeruginosa strains respond to sub‑MIC copper (Cu) and gentamicin (GE) stress, individually and in combination (Cu + GE). Across all strains, Cu acted as the dominant envelope‑active stressor, increasing biofilm biomass and extracellular DNA (eDNA) release, suppressing twitching and swarming motility, reducing quorum‑sensing‑linked protease activity, and enhancing pyomelanin production. GE alone produced limited physiological changes but modulated Cu‑driven outputs during co‑exposure, including attenuation of Cu‑induced eDNA release and strain‑specific shifts in motility and pigmentation. Early transcriptional profiling revealed consistent Cu‑dependent repression of lasI and mvfR, induction of the metal‑responsive regulator czcR, and downregulation of oprD under Cu or Cu + GE, corresponding to reduced imipenem inhibition zones when Cu was present during susceptibility testing. Combined Cu + GE exposure produced non‑additive, emergent effects that diverged from single‑stressor responses and varied across strains. These findings demonstrate that sub‑inhibitory Cu creates an envelope‑centered regulatory landscape into which gentamicin‑derived signals are integrated, generating heterogeneous and context‑dependent phenotypes. This work underscores the importance of metal-antibiotic interactions in shaping bacterial adaptation and highlights limitations of single‑stressor models for predicting antimicrobial behavior in combination.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"948-969"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397220","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

Insights into FACT in Cancers with Targeted Therapeutic Implications. 对靶向治疗癌症的FACT的见解。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-06-08 DOI: 10.1080/10985549.2026.2677550

Priyanka Barman, Sukesh R Bhaumik

引用次数: 0

Frequent Functional Orthology of Characterized Long Noncoding RNAs and Genomic Loci Associated with Complex Traits and Disorders. 特征长链非编码rna和与复杂性状和疾病相关的基因组位点的频繁功能Orthology。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-07-24 DOI: 10.1080/10985549.2026.2699150

Mitchell J Cummins, John S Mattick

{"title":"Frequent Functional Orthology of Characterized Long Noncoding RNAs and Genomic Loci Associated with Complex Traits and Disorders.","authors":"Mitchell J Cummins, John S Mattick","doi":"10.1080/10985549.2026.2699150","DOIUrl":"10.1080/10985549.2026.2699150","url":null,"abstract":"Genome wide association studies (GWAS) have identified many haplotype blocks linked to a wide range of complex human traits, including intelligence, neuropsychiatric disorders, and immunological disorders, among many others. Approximately a quarter of these haplotype blocks lack protein-coding sequences but most express long noncoding RNAs (lncRNAs). Here we show that human loci orthologous with mammalian lncRNAs involved in neurological or immunological functions are commonly associated with a human trait that is commensurate with the reported lncRNA function. We also show that for many neurological, autoimmune, and cancer complex traits, the vast majority (> 90%) of associated haplotype blocks express one or more lncRNAs. We present a database of lncRNAs expressed from human haplotype blocks associated with GWAS traits, with their putative mouse orthologs, as a resource for functional analysis. Our analyses establish a framework for investigating the molecular etiology of complex traits and suggest a general solution may exist to the challenge of diagnosing and treating many complex disorders.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1070-1089"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579436","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