Wiley Interdisciplinary Reviews: RNA最新文献

{"title":"Evolutionary Conservation and Functional Diversification of the Rbm24/38 Family in Metazoans.","authors":"Xiangmin Zhang, Ailong Zhang, Zongbao Bai, Hongyan Li","doi":"10.1002/wrna.70054","DOIUrl":"https://doi.org/10.1002/wrna.70054","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels and are essential mediators of post-transcriptional gene regulation in a wide range of physiological and pathological processes. The Rbm24/38 family is a conserved group of RRM-containing RBPs. In invertebrates, Rbm24/38 homologs are generally present as single-copy genes, whereas vertebrates possess two paralogs, Rbm24 and Rbm38, reflecting the progressive elaboration of posttranscriptional regulatory networks during evolution. Functional evidence for non-vertebrate Rbm24/38 homologs remains limited; the nematode protein SUP-12 has been primarily implicated in the regulation of pre-mRNA splicing during myogenesis. By contrast, vertebrate Rbm24 and Rbm38 exhibit broader spatial expression patterns across multiple tissues. Although their expression domains partially overlap, they also display clear gene- and species-specific differences. Functionally, vertebrate Rbm24 and Rbm38 contribute to multilayered post-transcriptional regulation through mechanisms such as alternative splicing, mRNA stability control, and alternative polyadenylation. In addition, regulatory features including isoform diversity, phase-separation potential, and post-translational modifications may further expand their functional versatility, enabling them to coordinate cell fate decisions and tissue homeostasis in distinct physiological contexts. In this review, we summarize recent advances in the evolution, structure, expression, molecular regulation, and biological functions of the Rbm24/38 family. We highlight its conserved features and functional diversification, as well as key unresolved questions regarding its evolution and specialization across metazoans.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70054"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765436","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}

{"title":"Shaping Spliceosome Dynamics Through Protein Arginine Methylation.","authors":"Sai Wu, Kelly Schneggenburger, Michael C Yu","doi":"10.1002/wrna.70056","DOIUrl":"10.1002/wrna.70056","url":null,"abstract":"<p><p>Accurate removal of intervening intronic sequences from pre-mRNA is required for proper eukaryotic gene expression. This process, termed pre-mRNA splicing, is carried out by a spliceosome, a dynamic RNA-protein macromolecular machinery. Proteomic studies have shown that many spliceosomal components and associated factors harbor protein arginine methylation, a type of post-translational modification. These findings raise the question of how arginine methylation influences the process or outcome of pre-mRNA splicing. Although targeted studies have provided important molecular insights into how this modification regulates splicing protein subcellular localization, abundance, RNA/protein interactions, and snRNP biogenesis, much remains unknown, especially given the large number of methylated proteins identified that have known roles in regulating pre-mRNA splicing. In this review, we summarize current knowledge of how protein arginine methylation contributes to pre-mRNA splicing and discuss how this modification may help tune the structural and functional plasticity of the spliceosome.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70056"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760611","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}

{"title":"tRNAs at the Virus-Host Interface.","authors":"Deeksha Madhry, Varsha Meena, Riya Roy, Areeba Aziz, Ravi Kumar Yelegara Siddappa, Bhupendra Verma","doi":"10.1002/wrna.70050","DOIUrl":"10.1002/wrna.70050","url":null,"abstract":"<p><p>The discovery of tRNA as an adapter molecule established the foundation for understanding its essential roles in gene expression, stress responses, cellular homeostasis, and disease, including viral infections. Human tRNAs carry multiple chemical modifications that maintain their structure and ensure proper function. Since viruses depend entirely on host translation machinery, many of them can manipulate tRNA functioning at the structural level or the functional level. This review highlights how diverse viruses exploit tRNA epitranscriptomics, supported by recent advances in tRNA sequencing and profiling. Understanding the mechanisms by which viruses exploit the host tRNA landscape and the related molecules can identify novel antiviral targets, offering opportunities to interfere with viral protein synthesis and replication.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70050"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13413254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148608089","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}

{"title":"Molecular Interplay of PARN and Telomerase: Tail Modifiers and Disease Implications.","authors":"Sujitha Felicitus, Shalon Suzanne Pinto, Sai Samanvitha Madagundapalli Ramakrishna, Dechamma Pandyanada Nanjappa, Gunimala Chakraborty, Anirban Chakraborty","doi":"10.1002/wrna.70049","DOIUrl":"10.1002/wrna.70049","url":null,"abstract":"<p><p>Poly(A)-specific ribonuclease (PARN) and telomerase are two indispensable tail-modifying enzymes that are required in two critical cellular processes: the control of the rate of RNA stability and maintenance of telomere integrity, respectively. Pathogenic variations in genes that code for PARN and telomerase complex enzymes have been implicated in several rare genetic diseases, including bone marrow failure syndromes, telomere biology-related disorders, and neoplastic ailments. This is further exemplified by defects in p53 signaling, which not only exacerbate the effects of telomere shortening but also negatively regulate PARN activity, thereby promoting cancer development and accelerated aging. This review examines the molecular interactions between PARN and telomerase, as well as their implications in disease development, with a focus on emerging therapeutic strategies that target the pathways regulated by these two enzymes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70049"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309774","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}

{"title":"Spatiotemporal Control of microRNA-Target Interactions.","authors":"Linh T T Le","doi":"10.1002/wrna.70053","DOIUrl":"10.1002/wrna.70053","url":null,"abstract":"<p><p>MicroRNA-mediated gene regulation occurs within spatially organized intracellular environments and is governed by dynamic molecular interactions that unfold across defined kinetic timescales. Although classical models emphasize sequence complementarity between microRNAs (miRNAs) and their target transcripts, growing evidence indicates that the outcomes of miRNA-target interactions vary widely across cellular contexts and cannot be explained solely by seed pairing or steady-state expression levels. These observations suggest that additional regulatory layers shape the efficiency and fate of miRNA-mediated silencing. In this Review, we examine how the spatial organization of the cell structures miRNA activity across distinct intracellular microenvironments, where the local availability of Argonaute (AGO)-containing RNA-induced silencing complexes (RISCs), target RNAs and regulatory cofactors influences the probability that RISCs encounter and productively engage their targets. We further explore the temporal dimension of miRNA regulation, including Argonaute loading and turnover, the dwell time of RISC-target interactions, miRNA stability and target transcript lifetimes. Recent advances in quantitative and high-resolution approaches for studying RNA dynamics in living cells are beginning to reveal these regulatory processes directly. Together, these observations support a spatiotemporal kinetic model of miRNA regulation, in which intracellular organization and molecular dynamics jointly determine the probability and efficiency of gene silencing. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70053"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702266","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}

{"title":"Noncoding RNAs and the Architecture of Gene Regulation: Focus on Long and Small Regulatory RNAs.","authors":"Samuel Z Desind, Samira K Bell, Carol S Lutz","doi":"10.1002/wrna.70051","DOIUrl":"10.1002/wrna.70051","url":null,"abstract":"<p><p>Noncoding RNAs (ncRNAs) are a diverse and abundant class of molecules that play essential roles in gene regulation across eukaryotic organisms, including roles in human homeostasis and disease. Historically regarded as transcriptional artifacts or byproducts, ncRNAs are now recognized as essential regulators of transcriptional and post-transcriptional processes that shape cellular homeostasis and disease phenotypes. We outline the historical discovery, classification, and functional diversification of many classes of ncRNAs, with a focus on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). We summarize the current understanding of miRNA and lncRNA biogenesis, processing, and key mechanisms of action, including miRNA-lncRNA interactions and structure-dependent regulatory functions of lncRNAs. Emphasis is placed on the dynamic interplay between lncRNAs and miRNAs, their roles in fine-tuning gene expression networks, and how advances in transcriptomics, chemical probing, and structural biology have transformed our understanding of ncRNA regulatory complexity. Finally, we summarize the current landscape of RNA therapeutics. This analysis maps the historical evolution of ncRNA biology, the establishment of ncRNAs as integral regulators of gene expression and disease phenotype, and the emerging prevalence of RNA-based therapeutic strategies.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70051"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456810","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}

{"title":"Beyond the Poly(A) Tail: The Expanding Functional Landscape of PABPN1 and Its Dysregulation in OPMD and Cancer.","authors":"Wen-Liang Guan","doi":"10.1002/wrna.70052","DOIUrl":"10.1002/wrna.70052","url":null,"abstract":"<p><p>Nuclear poly(A)-binding protein N1 (PABPN1) is a poly(A)-binding protein widely expressed in the nuclei of eukaryotic cells. As a key regulator of mRNA 3'-end processing, it participates not only in poly(A) tail synthesis and length regulation but also in alternative polyadenylation (APA). Recent studies have demonstrated that PABPN1 undergoes liquid-liquid phase separation (LLPS) to form dynamic membraneless compartments, such as nuclear speckles and nuclear poly(A) domains (NPADs), and contributes to its physiological functions. Emerging evidence has further implicated PABPN1 in a range of cellular processes. These include downstream consequences of APA dysregulation, such as altered stress responses and cell fate decisions, as well as APA-independent molecular functions, including its direct roles in DNA repair and cell cycle control. Dysregulation of PABPN1 LLPS, driven either by intrinsic expansion of its N-terminal alanine stretch or by altered interactions with regulatory cofactors, promotes a transition from dynamic liquid-like condensates to pathological solid-like aggregates. This phase transition is associated with the pathogenesis of oculopharyngeal muscular dystrophy (OPMD) and contributes to oncogenic APA patterns in various cancers. This review summarizes recent findings on the emerging physiological functions of PABPN1, its phase separation characteristics, and the molecular mechanisms underlying its transition into pathological aggregates.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 4","pages":"e70052"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473101","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}

{"title":"Exploring New Frontiers in Bone Metabolism: Role and Potential of lncRNA DANCR.","authors":"Mianmian Yang, Ruiqi Huang, Ruiming Wen, Haining Gao, Bo Chang, Xuejie Yi","doi":"10.1002/wrna.70047","DOIUrl":"10.1002/wrna.70047","url":null,"abstract":"<p><p>As an emerging epigenetic regulator, differentiation-antagonizing long-chain noncoding RNA (lncRNA) plays multiple roles in bone metabolism regulation and bone-related diseases. We found that lncRNA DANCR regulates bone metabolism by inhibiting bone formation and promoting resorption. Additionally, it plays a crucial role in chondrogenesis and maintaining bone homeostasis. Under pathological conditions, lncRNA DANCR is involved in osteoarthritis and osteoporosis progression and malignant development of osteosarcoma. Here, we summarize the multiple roles of lncRNA DANCR in bone metabolism, discuss the interactions of lncRNA DANCR with microRNAs and multiple signaling pathways, and construct a network framework for bone metabolism regulation. We conclude that lncRNA DANCR is a key regulator of exercise, pharmacological interventions, and polymeric compounds in combating bone diseases. These findings extend our understanding of the function of lncRNA DANCR and provide important clues for the development of further therapeutic strategies. This article is categorized under: RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 3","pages":"e70047"},"PeriodicalIF":4.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158331","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}

{"title":"Promoter-Targeting RNA Technologies: An Epigenetic Strategy for Gene Activation and Gene Silencing.","authors":"Rajat Hegde, Maryam Abdul Ajees, Kedlaya Srikrishna H Damodar, Esha Poojary, Smita Hegde, Shama Prasada Kabekkodu","doi":"10.1002/wrna.70043","DOIUrl":"10.1002/wrna.70043","url":null,"abstract":"<p><p>Promoter-targeted RNAs (PTRs) are emerging as a transformative approach for future therapeutics, offering the ability to directly modulate gene expression at the transcriptional level. Unlike traditional RNA-based methods that work post transcriptionally, PTRs interact with gene promoter regions to either activate or suppress gene transcription. This strategy offers a key advantage by enabling more stable and long-lasting control of gene expression, since it acts directly at the level of chromatin and epigenetic regulation rather than only degrading RNA or blocking translation. Unlike CRISPR-based methods, promoter-targeted RNAs alongside traditional siRNAs and ASOs provide a reversible and finely tuned way to reprogram the chromatin accessibility and histone modifications without making permanent changes to the genome. This review explores the broadening spectrum of PTRs modalities, including small activating RNAs, small interfering RNAs, promoter-targeted R-loop inducers, peptide nucleic acids, RNA aptamers, and triplex-forming RNAs. Several preclinical studies have demonstrated their ability to reactivate silenced tumor suppressor genes or downregulate oncogenes, offering targeted and reversible gene control. Notably, saRNAs like MTL-CEBPA (Phase II) and RAG-01 (Phase I) have reached clinical evaluation for liver and bladder cancer, highlighting their translational potential. However, efficient nuclear delivery, off-target effects, immune activation, and tumor heterogeneity remain the major concerns for clinical applications. Future progress in this field will depend on overcoming technical hurdles such as ensuring efficient nuclear delivery, improving chemical modifications to increase RNA stability, and designing delivery systems that combine tissue-specific targeting with precise transcriptional regulation. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 3","pages":"e70043"},"PeriodicalIF":4.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821554","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}

{"title":"Structural and Functional Diversity of RNA-Containing Toxin-Antitoxin Systems.","authors":"Harshita Dutta, Salik Noor, Kavyashree Nadig, Mahavir Singh","doi":"10.1002/wrna.70042","DOIUrl":"10.1002/wrna.70042","url":null,"abstract":"<p><p>Toxin-antitoxin (TA) systems are ubiquitous prokaryotic genetic modules located on plasmids and chromosomes, contributing to plasmid stabilization, maintenance of genome integrity, phage defense, and bacterial pathogenesis. Canonically, these systems encode a metabolically stable toxin and a labile antitoxin that neutralizes the toxin activity under homeostatic conditions. Stress-induced antitoxin degradation unleashes the toxin, leading to growth arrest through inhibition of various cellular processes, including translation, DNA replication, and cell wall synthesis. TA systems are classified into eight types (type I-VIII) based on antitoxin identity and mode of action. Among these, types I, III, and VIII represent RNA-containing TA systems in which either only antitoxin (types I and III) or both toxin and antitoxin (type VIII) are RNA molecules. Type I systems utilize small cis- or trans-encoded antisense RNA antitoxins that base-pair with toxin mRNAs to block translation or promote degradation; their toxins are typically small hydrophobic peptides targeting membranes or inducing nucleoid condensation. Type III systems encode endoribonuclease toxins and structured RNA antitoxins that assemble into stoichiometric ribonucleoprotein complexes. Structural studies of ToxIN, CptIN, and AbiF type III TA complexes have highlighted the pseudoknot and stem-loop containing antitoxins that engage toxin active sites with high specificity. Type VIII systems, such as CreTA, are fully RNA-based systems, where the toxin sequesters rare tRNAs and the antitoxin mimics CRISPR RNAs to mediate Cas-dependent transcriptional repression of the toxin. In this review, we summarize current understanding of these systems, emphasizing their molecular mechanisms of assembly and action and their emerging applications in biotechnology and therapeutics. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 3","pages":"e70042"},"PeriodicalIF":4.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821603","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}