RNA Biology最新文献

{"title":"RNA export through the nuclear pore complex: pathways, mechanisms, and imaging strategies.","authors":"Donghong Fu, Wenlan Yu, Fanghemei Zhang, Coby Rush, Mark Tingey, Weidong Yang","doi":"10.1080/15476286.2026.2656571","DOIUrl":"10.1080/15476286.2026.2656571","url":null,"abstract":"<p><p>Understanding how RNA molecules traverse the nuclear pore complex (NPC) is central to regulated gene expression because the NPC serves as the selective gateway for RNA export from the nucleus. Distinct RNA classes, including tRNAs, snRNAs, miRNAs, lncRNAs, piRNAs, rRNAs, mRNAs, and circRNAs, follow biogenesis-coupled pathways and engage specific transport receptors and accessory factors to cross this barrier. Recent advances in single-molecule and super-resolution microscopy now enable direct, NPC-resolved visualization of transport for selected RNA species, allowing quantitative measurements of export kinetics, 3D trajectories through the pore, and interaction dynamics with NPC substructures. Here, we review and compare what has been learned from NPC-resolved imaging across RNA classes studied to date, highlighting both shared organizing principles and cargo-specific behaviours. We then describe an experimental and analytical toolbox for NPC-resolved studies of mRNA and pre-ribosomal particle export, including RNA-labelling strategies, major single-molecule and super-resolution modalities, and quantitative metrics used to extract transport parameters. Finally, we discuss key technical and conceptual barriers that currently limit extension to other RNA classes, particularly small and/or low-abundance RNAs, and outline practical strategies to overcome these constraints. Together, this review provides a unified framework for the next generation of single-molecule dissection of RNA dynamics at the nuclear pore.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-32"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating ribosome biogenesis disorders through structural biology.","authors":"Sameer Singh, Denis L J Lafontaine","doi":"10.1080/15476286.2026.2701521","DOIUrl":"10.1080/15476286.2026.2701521","url":null,"abstract":"<p><p>Ribosomes are essential nanomachines responsible for synthesizing all cellular proteins. Their production, known as ribosome biogenesis, is a highly complex and energy-intensive process that requires the coordinated action of hundreds of proteins and RNA-based <i>trans</i>-acting factors to assemble and mature the functional ribosomal components. Ribosome biogenesis is increasingly recognized as a key contributor to human disease: excessive ribosome production can fuel tumorigenesis, while insufficient or defective ribosome production is observed in a group of tissue-specific disorders known as ribosomopathies. Although the basis of this tissue specificity remains poorly understood, the most commonly affected systems are the blood, brain, and bones. Recent advances in structural biology have yielded high-resolution snapshots of precursor (pre-)ribosomes at various stages of maturation, offering new insights into how pathogenic variants of ribosomal proteins or assembly factors disrupt critical molecular interactions. In this review, we highlight selected examples where structural information is beginning to illuminate the molecular basis of ribosomopathies.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-12"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating bulk and single-cell transcriptomic data to construct a risk model for histidine metabolism-related epithelial cell features in lung adenocarcinoma, predicting prognosis and immune landscape.","authors":"Chaofan Mao, Lin Zhou","doi":"10.1080/15476286.2026.2662721","DOIUrl":"10.1080/15476286.2026.2662721","url":null,"abstract":"<p><p>The rising incidence and mortality of lung adenocarcinoma (LUAD) present a significant public health challenge. Histidine, an essential amino acid, plays a pivotal role in metabolic processes, yet its specific contribution to LUAD pathogenesis remains to be elucidated. This study obtained bulk and single-cell RNA sequencing (scRNA-seq) data for LUAD from UCSC Xena and Code Ocean platforms, respectively. By integrating differential expression analysis, univariate/multivariate Cox analysis, and LASSO regression analysis, prognostic genes for LUAD were identified, and a prognostic risk model was constructed. Algorithms including ESTIMATE, ssGSEA, and CIBERSORT were employed to investigate immune heterogeneity across different groups. Furthermore, molecular subtypes of LUAD were identified through consensus clustering. This study, through the integration of bulk and scRNA-seq data, identified epithelial cells as the key effector cell population in LUAD, which can be further subdivided into four functionally heterogeneous subpopulations. Seven histidine metabolism-related epithelial cell-specific genes with prognostic significance in LUAD were identified (WIF1, GATA2, CD69, ID1, C4BPA, WFDC2, and CCL20), enabling the construction of a robust prognostic risk model. Immune infiltration analysis revealed that low-risk patients exhibited more robust immune infiltration and activity. Furthermore, cross-cancer exploratory evidence suggested potential sensitivity to CTLA-4 and PD-L1 inhibitors in this group. Furthermore, consensus clustering analysis successfully partitioned LUAD into two molecular subtypes exhibiting immune heterogeneity. The prognostic model constructed based on epithelial cell-specific genes associated with histidine metabolism effectively distinguishes LUAD patients and their immune characteristics, revealing epithelial cells as a key cell population regulating LUAD histidine metabolism.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-17"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profound alterations of cancer transcriptomes by the RNase L inhibitor ABCE1 through the modulation of UU/UA-dinucleotide rich transcript abundance.","authors":"Edward Hitti, Tala Bakheet, Linah Mahmoud, Nada Al-Mutairi, Latifa Alhaj, Fahad Al-Zoghaibi, Khalid S A Khabar","doi":"10.1080/15476286.2026.2629475","DOIUrl":"10.1080/15476286.2026.2629475","url":null,"abstract":"<p><p>Tumorigenesis is commonly driven by genetic mutations and disruptions in cellular signalling pathways. Here we show that the oncogenic overexpression of the RNase L inhibitor ABCE1, a component of interferon signalling, leads to distinct and extensive deviations in cancer transcriptomes. RNase L is a cellular endonuclease that cleaves RNA molecules at specific UU and UA dinucleotide sites. Typically, it is activated by viral infections and interferon signalling leading to targeting and destruction of UU/UA-rich viral and cellular mRNA. RNase L has also homoeostatic and tumour suppressive roles. Relying on patient transcriptomic data, we show that ABCE1 is extensively overexpressed in colorectal cancer (CRC) and to a lesser extent in lung cancer. This upregulation was strongly associated with the co-upregulation of almost all UU/UA rich transcripts and downregulation of those that are UU/UA-poor. Many of upregulated mRNAs code for proteins involved in cell cycle regulation and mitosis. Accordingly, the knockdown of ABCE1 in the CRC cell line HT29 led to reduced proliferation. Surprisingly, the very high ABCE1 levels were associated with improved patient survival in CRC. This observation might be related to an anti-ABCE1-specific immune response due to the induction of tumour-reactive cytotoxic T lymphocytes by ABCE1 as previously reported. In lung cancer ABCE1 overexpression is milder and is associated with poor survival. We report a measurable, specific, and extensive modulation of cancer transcriptomes by the oncogenic overexpression of a component of interferon signalling with unexpected outcomes on patient survival.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-14"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00852 inhibits colorectal cancer progression by regulating cell apoptosis, epithelial‒mesenchymal transition, invasion, and cuproptosis through miR-1276/LACTB.","authors":"Chun-Xiao Wang, Xiao-Jing Chen, Ling Zeng, Wang-Wu Liu, Jia-Sheng Ke, Yu-Ze Wu, Xian Deng, Yi Qiu, Ming-Liang Chen, Zhong-Shi Hong, Cheng-Zhi Qiu","doi":"10.1080/15476286.2026.2640489","DOIUrl":"10.1080/15476286.2026.2640489","url":null,"abstract":"<p><p>Exploring the role of key genes in colorectal cancer (CRC) progression to identify effective targets is highly practical. Previous studies have shown that miR-1276/ACTB plays an important regulatory role in CRC. In addition to miRNA, lncRNA also play a crucial role in tumour progression. However, there are currently no studies exploring the relationship between lncRNAs and miR-1276/LACTB. Analysis of the relationship between lncRNAs and miR-1276 using ENCORI database showed that lncRNA-LINC00852 bound to miR-1276 and inhibited its expression, thereby promoting LACTB expression, and miR-1276 upregulation weakened the ability of LINC00852 to promote LACTB expression. ENCORI and TCGA data also indicated that the expression of LINC00852 and LACTB in CRC was significantly downregulated, while miR-1276 expression was significantly upregulated. LINC00852 overexpression promoted E-cadherin expression, increased the activities of Caspase-3/8/9 and PARP, inhibited the expression of N-cadherin and Vimentin, and decreased the expression and secretion of MMP-2 and MMP-9. LINC00852 inhibited CRC cell viability, invasion and migration while promoting apoptosis. miR-1276 overexpression or LACTB knockdown significantly blocked the regulatory effect of LINC00852 on CRC cell biological function. Further xenograft mouse model confirmed that LINC00852 downregulated miR-1276 expression, enhanced the expression of LACTB and FDX1, increased tumour copper levels and inhibited tumour formation, indicating that the anticancer effect of LINC00852/LACTB may also be related to cuproptosis. However, LACTB knockdown blocked the inhibitory effect of LINC00852 on tumour formation. Therefore, LINC00852 inhibits CRC progression through miR-1276/LACTB, indicating that LINC00852/miR-1276/LACTB axis is an important pathway closely related to the occurrence and development of CRC.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-15"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA functions in HIV-1 infection.","authors":"Gabriela Berger, Y Grace Chen","doi":"10.1080/15476286.2026.2722169","DOIUrl":"https://doi.org/10.1080/15476286.2026.2722169","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are covalently closed RNA molecules with increasingly recognized roles in post-transcriptional gene regulation, immune signalling, and host-pathogen interactions. Although circRNAs have been characterized across diverse biological contexts, their roles in viral infection, particularly HIV-1, remain an underexplored area of RNA biology. Here, we review current knowledge of circRNA function in HIV-1 infection, organized into three major themes. First, we examine host-derived circRNAs, which are broadly dysregulated during infection and correlate with viral load, immune status, and antiretroviral therapy response. Second, we discuss viral-derived circRNAs, highlighting emerging evidence that HIV-1 encodes functional circRNA isoforms capable of modulating viral replication and transcription. Finally, we review synthetic circRNA-based approaches that exploit key viral RNA-protein interactions as potential antiviral tools. Collectively, these findings underscore the expanding functional roles of circRNAs in HIV-1 infection and highlight their potential as both therapeutic targets and molecular tools for future research.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"23 1","pages":"1-14"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PrfH accelerates repair of colicin E3 - damaged translating ribosomes by RtcB2.","authors":"Tinashe P Maviza, Nadezhda R Burmistrova, Aleksandr A Grachev, Elizaveta Khisambeeva, Dmitrii I Shiriaev, Anastasiia S Zarechenskaia, Alena Paleskava, Andrey L Konevega, Olga A Dontsova, Petr V Sergiev","doi":"10.1080/15476286.2026.2669700","DOIUrl":"10.1080/15476286.2026.2669700","url":null,"abstract":"<p><p>Colicin E3 (E3-rRNAse) abolishes protein biosynthesis in bacteria by cleaving 16S rRNA in the decoding centre. The RtcB2-PrfH 16S rRNA repair module prevents cellular death upon exposure to E3-rRNAse in <i>E. coli</i>. Upon overexpression, RtcB2 RNA ligase alone was capable of relieving <i>E. coli</i> growth, which was inhibited by E3-rRNAse. Using <i>in vitro</i> ribosome repair system based on recombinant components, we demonstrated that RtcB2 alone could repair E3-rRNAse cleaved 30S subunits and 70S ribosomes. The peptide chain release factor homolog (PrfH), which is able to hydrolyse peptidyl-tRNA bound by colicin-cleaved ribosomes, boosts RtcB2 ligation efficiency for damaged ribosomes engaged in translation.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-10"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin remodelling: a driving force in reverse mechanotransduction.","authors":"Julie Buisson, Florent Colin, Anna Labernadie, Morgane Rabineau, Dominique Vautier","doi":"10.1080/15476286.2026.2678068","DOIUrl":"10.1080/15476286.2026.2678068","url":null,"abstract":"<p><p>Chromatin serves as the dynamic carrier of genetic and epigenetic information in eukaryotic cells, playing a pivotal role in maintaining nuclear shape, mechanical stability, and cellular function. Aberrant nuclear morphology, often observed in mechanically stressed environments or diseases such as progeria and muscular dystrophy, correlates with nuclear dysfunction, DNA damage, and disrupted mechanotransduction. Chromatin exists in two main configurations - compacted heterochromatin and decompacted euchromatin - each regulating gene expression and cellular behaviour through epigenetic modifications. Histone acetyltransferases and deacetylases modulate chromatin compaction, while histone methylation introduces further regulatory complexity. Chromatin's viscoelastic properties enable it to store and restore mechanical energy, acting as a mechanosensitive component within the nucleus. External forces propagate from the extracellular matrix through focal adhesions, the cytoskeleton, and the nuclear lamina to chromatin, forming a direct mechanotransduction pathway. However, the reverse pathway - how internal nuclear forces generated during chromatin remodelling influence the nuclear membrane, cytoskeleton, and cell adhesion - remains poorly understood. This review explores the role of chromatin as a tensegrity element, capable of generating mechanical forces through condensate formation. It examines evidence supporting chromatin decompaction as a regulator of reverse mechanotransduction and identifies potential mechanical partners involved in this process. Understanding these mechanisms may elucidate how chromatin dynamics contribute to cellular fate decisions and disease pathogenesis.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-22"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of proteins exhibiting <i>in vitro</i> RNA chaperone activity through gradient profiling in the Lyme disease spirochete, <i>Borrelia burgdorferi</i>.","authors":"Taylor Van Gundy, Cornelius Schneider, Christopher C Ebmeier, Gavin Z Chambers, Nicholas A Cramer, Kathryn Mf Chambers, Dan Drecktrah, Jenny A Hyde, Jon T Skare, Richard T Marconi, D Scott Samuels, Meghan C Lybecker","doi":"10.1080/15476286.2026.2684395","DOIUrl":"10.1080/15476286.2026.2684395","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) play key roles in regulating gene expression across all domains of life. However, relatively few RBPs have been discovered and characterized in <i>Borrelia</i> (<i>Borreliella</i>) <i>burgdorferi</i>, the causative agent of Lyme disease. We utilized gradient profiling to identify putative RBPs that co-sediment with small RNAs (sRNAs) and nascent mRNAs. The previously hypothetical proteins BB0749, BB0713 and BB0796, as well as the chemotaxis-related protein CheY2 and the flagella-associated protein FlgV demonstrated RNA unwinding (structural remodeling), RNA annealing, and strand displacement activity. Moreover, <i>in vivo</i> co-IP assays demonstrated BB0749 binds RNA in <i>B. burgdorferi</i>.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-23"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-like subunits of multisubunit RNA polymerases: insights into structure, function, and disease.","authors":"Onyinyechi C Onuoha, Alana E Belkevich, Ryan J Palumbo, Bruce A Knutson","doi":"10.1080/15476286.2026.2700806","DOIUrl":"10.1080/15476286.2026.2700806","url":null,"abstract":"<p><p>Multisubunit RNA polymerases share a deeply conserved architectural core, yet their regulatory complexity has expanded dramatically over evolution. At the heart of this architecture lies an ancient assembly module formed by the alpha and alpha-like subunits. Originally emerging as a homodimeric scaffold in bacteria, this module was duplicated and partitioned into asymmetric heterodimers in archaea and eukaryotes. Far from serving as inert structural elements, alpha-like subunits function as organizational hubs that coordinate polymerase biogenesis, interface with initiation and regulatory factors, and-in some contexts-operate outside the holoenzyme to influence RNA processing and growth signalling pathways. Recent structural and genetic studies reveal that although the α-motif-mediated dimerization framework is highly conserved, species- and polymerase-specific tuning of alpha-like subunit interaction surfaces has generated functional diversification, with important consequences for assembly fidelity, transcriptional regulation, and disease susceptibility. Mutations in alpha-like subunits shared between RNAPI and RNAPIII underlie a ribosomopathy and leukodystrophy, while altered dosage contributes to oncogenic growth programmes and proliferative signalling. These findings highlight alpha-like subunits as evolutionarily conserved yet adaptable platforms that couple transcriptional capacity to developmental and metabolic demands. By integrating structural, evolutionary, mechanistic, and clinical evidence, this review described the alpha-like subunits as central regulators of polymerase function and as emerging determinants of transcription-linked disease.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-18"},"PeriodicalIF":4.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}