Wiley Interdisciplinary Reviews: RNA最新文献

{"title":"Functional Inclusion of RNA Biology in the Tethered Extracellular Matrix.","authors":"Peiyuan Chai, Ryan A Flynn","doi":"10.1002/wrna.70048","DOIUrl":"10.1002/wrna.70048","url":null,"abstract":"<p><p>RNA biology is traditionally confined to the cytosolic and nuclear spaces, where it plays critical roles across nearly all biochemical processes. Our recent observation of spatiotemporal regulation of cell surface ribonucleoproteins, consisting of glycoRNA and RNA-binding proteins, by heparan sulfate expands this knowledge to the extracellular matrix (ECM). We identified VEGF-A as a new noncanonical cell surface RNA-binding protein through the arginine residues within the heparan sulfate binding domain. The interaction between VEGF-A and cell surface RNA as a polyanion in the ECM provides an expanded example of the cell surface RNA interactome. Here, we review the common features of the heparan sulfate-binding domain and RNA-binding domain to provide a logical and testable path toward understanding the regulation and function of cell surface glycoRNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 3","pages":"e70048"},"PeriodicalIF":4.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043982","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":"Therapeutic Prospects of Artificially Synthesized Circular RNA.","authors":"Hui Chen, Yi Du, Yesheng Wang, Xue Zhang, Maolei Zhang, Xingguo Liang, Qiyi Zhao, Ming Liu","doi":"10.1002/wrna.70039","DOIUrl":"10.1002/wrna.70039","url":null,"abstract":"<p><p>Endogenous circRNAs play crucial physiological roles within organisms and hold significant potential as biomarkers for disease diagnosis, prognosis, and therapeutic targeting. The closed-loop structure of circRNAs confers unique advantages in stability, making them ideal candidates for programmable delivery vectors and platforms for drug delivery and therapeutic applications. Various artificial synthesis techniques have been developed to ensure a reliable supply of engineered circular RNAs, thereby enabling the creation of novel drugs and therapies. However, there remains a notable absence of a systematic summary regarding the landscape and emerging trends of artificially synthesized circular RNAs. In this review, we provide a comprehensive overview of the preparation and purification methods, sequence design and optimization strategies, delivery technologies, quality control, application scenarios, as well as the progress in pre-clinical and clinical research on drugs and therapies related to artificially synthesized circular RNAs. Building upon this foundation, we conducted an in-depth analysis of the clinical translation hurdles and forthcoming trends in this field. We believe that clinical applications of circular RNAs as therapeutic approaches are promising after experts and scholars in both scientific research area and industry strengthen their collaboration. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease Translation > Mechanisms.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 2","pages":"e70039"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522306","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":"LncRNA PCAT18: Roles and Mechanisms in Human Cancers.","authors":"Xiaohui Wang, Henan Zhang, Fang Chen, Xujian Jiang, Qiang Zhang, Jihong Zhang","doi":"10.1002/wrna.70041","DOIUrl":"10.1002/wrna.70041","url":null,"abstract":"<p><p>lncRNAs are a group of RNA molecules with over 200 nucleotides involved in many biological processes. The dysregulation of lncRNA has been covered in several processes related to carcinogenesis, such as proliferation, apoptosis, invasion, evasion, and metastasis of cancer cells. PCAT18 is a newly discovered non-coding RNA first described as an androgen-regulated gene and highly upregulated in PCa. Recent studies revealed that PCAT18 functions as a regulatory molecule in PCa, lung cancer, breast cancer, digestive cancer, and leukemia. With this, we review the molecular mechanism and clinical significance of PCAT18 in various cancers. This article is categorized under: RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 2","pages":"e70041"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783117","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":"Stunning Intricacies of RNA Editing Complexes RECC, RESC, and REH2C: Functional Organization, Developmental Regulation, and Evolutionary History in Kinetoplastid Protists.","authors":"Suzanne M McDermott, Julius Lukeš, Laurie K Read, Reza Salavati, Achim Schnaufer, Sara L Zimmer, Jason Carnes, Alasdair Ivens, Naghmeh Poorinmohammad, Nicholas J Savill, Dave Speijer, Ken Stuart, Kristína Záhonová, Poorya Mirzavand Borujeni, Zihao Chen, Cody Goode, Sunil Kumar Sharma, Lars O'Hara, Jorge Cruz-Reyes","doi":"10.1002/wrna.70037","DOIUrl":"10.1002/wrna.70037","url":null,"abstract":"<p><p>RNA metabolism in kinetoplastid protists (Kinetoplastea), including trypanosomes and Leishmania, involves unique post-transcriptional mitochondrial RNA editing that creates translatable mRNAs through uridine (U) insertions and deletions (U-indels) directed by antisense guide RNAs (gRNAs). Like other biological processes that require specific RNA targeting, this system faces several challenges beyond coordinating its many components: assembling mRNA-gRNA hybrids, recognizing hundreds of sites, and accurately distinguishing pre-edited, partially edited, and fully edited transcripts in the mitochondrial environment. In parasites such as Trypanosoma brucei, significant energetic adaptations to different host environments also involve critical editing changes during development. The editing holoenzyme includes three molecular complexes and isoforms that carry most proteins: RNA Editing Catalytic Complexes (RECCs), which catalyze U-indel cycles; RNA Editing Substrate Complexes (RESCs), which serve as scaffolds to coordinate the editing components; and the RNA Editing Helicase 2 Complex (REH2C), which contains key proteins involved in developmental editing regulation. However, more proteins and functions are being discovered. The editing system, best understood in T. brucei, shows considerable evolutionary conservation in its core machinery; however, it varies in the extent of RNA editing and the organization of mitochondrial mRNA and gRNA genes across different species. Here we explore recent progress in our understanding of RNA editing and the growing use of modern computational tools, including artificial intelligence (AI) and structural methods, to examine function, organization, developmental regulation, and evolutionary aspects of this amazing system. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Processing > RNA Editing and Modification.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 2","pages":"e70037"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12936278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310820","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":"MiRNA Stability and Degradation: Dynamic Regulators of Cellular Regulatory Networks.","authors":"Ziqi Lin, Weijie Wen, Muhammad Irfan, Tielong Xu, Xianfeng Zhou","doi":"10.1002/wrna.70036","DOIUrl":"10.1002/wrna.70036","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are pivotal post-transcriptional regulators of gene networks in development and disease, with their functional output critically dependent on dynamic turnover. Dysregulation of miRNA turnover disrupts signaling fidelity and contributes to pathologies such as cancer and infection. This review synthesizes recent advances in understanding miRNA turnover, focusing on key degradation pathways-including ZSWIM8-mediated target-directed miRNA decay (TDMD), TUT4/7-DIS3L2-driven uridylation, and nuclease cleavage-and how they integrate with stability factors such as AGO association, terminal modifications, and sequence features to orchestrate global miRNA abundance and health status. From these insights, critical unresolved questions are delineated, such as identifying nucleases responsible for degrading TDMD-liberated miRNAs and elucidating compartment-specific degradation mechanisms in physiological contexts like the gut lumen and circulation. Addressing these questions will facilitate innovative strategies for targeting miRNA stability within precision medicine. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 1","pages":"e70036"},"PeriodicalIF":4.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087441","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":"3' Processing of Animal Replication-Dependent Histone mRNAs.","authors":"William F Marzluff","doi":"10.1002/wrna.70035","DOIUrl":"10.1002/wrna.70035","url":null,"abstract":"<p><p>Each time a eucaryotic cell divides, it replicates its DNA and packages the DNA into chormatin. Large amounts of all five histone proteins are co-ordinately synthesized to assemble the newly replicated chromatin. The metazoan replication-dependent (RD) histone mRNAs differ from all other cellular mRNAs. They are not polyadenylated, but end instead in a conserved stem-loop (SL). The genes encoding all five RD-histone mRNAs are clustered, and localized to a subdomain of the nucleus, the histone locus body (HLB). Factors required for transcription and 3' processing are concentrated in the HLB, allowing coordinate expression of the five histone mRNAs, which are synthesized inside the HLB. Since RD-histone genes lack introns, capping and 3' end formation are the only processing reactions required for their biosynthesis. A set of factors involved only in histone mRNA metabolism; NPAT, FLASH, U7 snRNP, and SLBP are required for synthesis of histone mRNAs. The HLB is present throughout the cell cycle. Histone mRNA expression is restricted to S-phase by phosphorylation of NPAT by cyclin E/cdk2. Like cleavage/polyadenylation, histone pre-mRNA processing requires recognition of a 5' signal, the SL, by SLBP, and a 3' signal, the histone downstream element (HDE) by U7 snRNP, with cleavage occurring between them. A subcomplex of CPSF, the cleavage module for cleavage/polyadenylation, is a component of the active U7 snRNP, which assembles in the HLB only in S-phase. CPSF73 catalyzes the cleavage of the nascent transcript to produce mature histone mRNA.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 1","pages":"e70035"},"PeriodicalIF":4.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067615","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":"Comprehensive Overview of Computational Tools for Alternative Splicing Analysis.","authors":"Hieu Tran, Nirad Banskota, Myriam Gorospe, Supriyo De","doi":"10.1002/wrna.70030","DOIUrl":"10.1002/wrna.70030","url":null,"abstract":"<p><p>Alternative splicing (AS) is a fundamental mechanism that generates transcriptomic diversity by selectively including or excluding exons and introns from pre-mRNA transcripts, leading to the production of multiple protein isoforms from a single gene. This process plays a crucial role in cellular differentiation, tissue specificity, and response to environmental stimuli. Given that it enables organisms to adapt to varying conditions and maintain homeostasis, AS has become a pivotal area of study in molecular biology. The advancement of RNA-sequencing (RNA-seq) technologies has propelled the development of sophisticated tools designed to detect and analyze various AS events. These tools have become indispensable for researchers seeking to unravel the complexities of AS and its implications in health and disease. In this review, we delve into the prominent alternative splicing analysis tools rMATS, SUPPA2, LeafCutter, MISO, DEXSeq, MAJIQ, StringTie, and Cufflinks, discussing their strengths, limitations, and practical usability. Each of these tools offers unique functionalities tailored to different aspects of AS analysis, and their usefulness varies depending on computational requirements, ease of use, and the specificity of the AS events they detect. Through careful consideration of the functionalities and limitations of these tools, we offer insights into the biological contexts for which they might be best suited for AS analysis. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Processing > Splicing Regulation/Alternative Splicing.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 6","pages":"e70030"},"PeriodicalIF":4.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12669084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655834","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":"Mixed Messages: Dynamic and Compositional Heterogeneity of Nuclear Messenger Ribonucleoprotein (mRNP) Complexes.","authors":"Theresa Wechsler, Ryuta Asada, Ben Montpetit","doi":"10.1002/wrna.70032","DOIUrl":"10.1002/wrna.70032","url":null,"abstract":"<p><p>Messenger ribonucleoprotein (mRNP) complexes assemble co-transcriptionally in the nucleus as RNA-binding proteins (RBPs) engage nascent transcripts. Ongoing RNA processing and RBP dynamics generate a diverse set of mRNPs, often producing a mature mRNA-capped, spliced, and polyadenylated-within a compact mRNP particle poised for nuclear export. The processing, packaging, and export of nuclear mRNPs are tightly regulated to ensure the fidelity of gene expression and to reprogram cellular function under changing organismal and environmental conditions. Understanding the compositional and organizational dynamics of nuclear mRNP assembly and maturation is essential, as dysregulation is linked to viral infections and a range of human diseases, including neurological disorders and cancer. Recent structural, biochemical, and in-cell studies have revealed key roles for the evolutionarily conserved Yra1/ALYREF proteins and the TRanscription-EXport (TREX) complex in mRNP packaging and export, highlighting broadly conserved functions across eukaryotes. While many questions remain, these advances have deepened our understanding of nuclear mRNA metabolism and offer new opportunities to investigate how disruptions in mRNA biogenesis and export factors, and their associated processes, contribute to disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Export and Localization > Nuclear Export/Import.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 6","pages":"e70032"},"PeriodicalIF":4.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12569565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145393458","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":"Conserved Functions of LARP1 Proteins in Eukaryotes.","authors":"Farnaz Mansouri-Noori, Mark A Bayfield","doi":"10.1002/wrna.70033","DOIUrl":"10.1002/wrna.70033","url":null,"abstract":"<p><p>La and La-related proteins (LARPs) are conserved RNA-binding proteins that share a characteristic La motif (LaM) and have important functions in RNA metabolism. Members of the LARP1 family bind a cohort of mRNAs encoding factors involved in the process of mRNA translation, including ribosomal protein mRNAs (RP mRNAs). These mRNAs can contain a sequence of 5-15 pyrimidines in their 5'UTRs, immediately following the m⁷G cap, and are named 5' terminal oligopyrimidine (5'TOP) mRNAs. The DM15 domain of human LARP1 has been suggested to specifically recognize this motif, thereby affecting 5'TOP mRNA translation and stability. However, the specific function of LARP1 in this context remains unclear. Intriguingly, the 5'TOP motif is not found in RP mRNAs in C. elegans and yeast, while LARP1 orthologs in some systems lack the characteristic DM15 domain, suggesting that essential functions of LARP1 family members may precede the emergence of the 5'TOP motif and the DM15. In this work, we review studies in humans and several model organisms where we draw parallels between reported RNA binding modes and functions of different LARP1 orthologs. We further present common themes and areas for further investigation. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 6","pages":"e70033"},"PeriodicalIF":4.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597601","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":"Potential Function of Glycosylated RNA in Diseases.","authors":"XiaoLing Chen, Quandan Tan, GuoLiang Zhu, Ping Ni, Song He, FengKai Mao, HongWei Deng, YaPeng Lin, Ying Luo, KeJie Chen, JunLi Hao, Jie Yang","doi":"10.1002/wrna.70031","DOIUrl":"https://doi.org/10.1002/wrna.70031","url":null,"abstract":"<p><p>This article reviews the potential role of glycosylated RNA (glycoRNA), a new form of RNA epigenetic modification, in diseases. GlycoRNA has two types of modifications, N-glycosylation and O-glycosylation, and is widely present on the surface of many tissues and cells. Early studies have shown that glycoRNA can bind to molecules such as siglec receptors, P-selectin, and RNA-binding proteins (RBPs), thereby mediating intercellular interactions and participating in various pathological processes, including tumor proliferation and metastasis, as well as cardiovascular and cerebrovascular inflammatory responses and immune regulation. Although current research faces challenges such as unclear glycosylation mechanisms, limited detection techniques, and difficulties in clinical translation, glycoRNA still shows potential as a new biomarker and therapeutic target. Future research is expected to elucidate its molecular mechanisms further and promote its application in disease diagnosis and treatment. This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 6","pages":"e70031"},"PeriodicalIF":4.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401827","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}