Wiley Interdisciplinary Reviews: RNA最新文献

{"title":"MicroRNAs and Cancer Racial Disparities.","authors":"Dan Zhao, Yifei Wang","doi":"10.1002/wrna.70028","DOIUrl":"10.1002/wrna.70028","url":null,"abstract":"<p><p>Cancer remains one of the leading causes of death worldwide. Despite various efforts to reduce cancer mortality, such as decreasing tobacco use, improving early detection and prevention methods, and enhancing cancer care and treatments, certain racial and ethnic groups continue to experience higher cancer incidence and mortality rates, along with shorter survival compared to other groups. Several factors, including socioeconomic status, environmental influences, diet, and behavior, contribute to these racial disparities. More importantly, scientists have identified a genetic basis for these observations, with a growing body of research highlighting microRNAs as significant players in cancer racial disparities. This review focuses on various types of microRNAs (such as epigenetically regulated, copy number altered, circulating, and exosomal) and microRNA single-nucleotide variations in the context of cancer-related racial disparities. Additionally, we have summarized the existing resources, including racial-specific model cell lines and cancer cohorts that include patients from diverse racial and ethnic backgrounds. Moreover, we provide here several key things to consider for future investigations. While many challenges remain, we aim to offer a balanced overview of this field to help scientists with varying expertise address these issues. This article is categorized under: RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 5","pages":"e70028"},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150292","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":"Natural Antioxidants as Regulators of Circular RNA Expression and Function.","authors":"Aseela Fathima, Shadiya Fawzu Ameer, Rabia Ilhem Kerzabi, Roberta Giordo, Gheyath K Nasrallah, Hatem Zayed, Gianfranco Pintus","doi":"10.1002/wrna.70023","DOIUrl":"10.1002/wrna.70023","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a class of noncoding RNAs characterized by covalently closed loop structures that confer high stability and diverse regulatory functions. Emerging evidence suggests that circRNAs modulate gene expression by acting as miRNA sponges, interacting with RNA-binding proteins (RBPs), influencing transcription, and serving as translational templates. Their dysregulation has been linked to various diseases, including cancer, cardiovascular, neurodegenerative, and metabolic disorders. Oxidative stress, a common hallmark in these pathologies, can alter circRNA expression and function. Natural antioxidants, derived from dietary sources such as fruits, vegetables, herbs, and medicinal plants, offer a promising approach for restoring redox homeostasis and influencing the regulation of circRNA networks. This review provides a comprehensive overview of how different classes of natural antioxidants, including flavonoids, polyphenols, carotenoids, terpenoids, vitamins, and alkaloids, modulate circRNA expression and function in various disease contexts. Representative compounds such as quercetin, curcumin, resveratrol, astaxanthin, kaempferol, and genistein exhibit circRNA-mediated actions that impact oxidative stress, inflammation, cell proliferation, apoptosis, and differentiation. The molecular mechanisms involve circRNA-miRNA-mRNA axes, interactions with RBPs, and modulation of epigenetic regulators and signaling pathways. We also discuss key challenges, including limited mechanistic understanding, bioavailability constraints, and the need for in vivo validation. Future perspectives emphasize the integration of antioxidant therapy with RNA-targeted approaches, advanced delivery systems, and personalized profiling of circRNA. Collectively, the regulatory interplay between natural antioxidants and circRNAs represents a promising frontier in redox biology and RNA-based therapeutics. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70023"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837942","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":"Emerging Roles of Biomolecular Condensates in Pre-mRNA 3' End Processing.","authors":"Yoseop Yoon, Liang Liu, Cailyx Quan, Yongsheng Shi","doi":"10.1002/wrna.70024","DOIUrl":"10.1002/wrna.70024","url":null,"abstract":"<p><p>Biomolecular condensates are membraneless assemblies of proteins and nucleic acids, often formed through liquid-liquid phase separation. They selectively concentrate specific biomolecules and play essential roles in diverse cellular processes and diseases. This review discusses the emerging roles of biomolecular condensates in pre-mRNA 3' end processing, a critical step in mRNA biogenesis. 3' end processing factors are enriched in intrinsically disordered regions and undergo phase separation to form condensates that, in turn, fine-tune the efficiency and specificity of 3' end processing. Additionally, we describe how distinct 3' end processing pathways are spatially and functionally compartmentalized within nuclear biomolecular condensates, such as nuclear speckles and histone locus bodies. Finally, we propose that 3' end processing represents a promising experimental system to investigate fundamental principles underlying biomolecular condensate formation and function. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70024"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849261","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":"Translation Reprogramming Caused by tRNA Modifications Represents a New Therapeutic Target for Cancer Treatment.","authors":"Yan Hu, Ziqi Liu, Hongke Qu, Mei Yang, Daixi Ren, Yumeng Liu, Lvyuan Li, Ming Tan, Can Guo, Wei Xiong, Zhaoyang Zeng","doi":"10.1002/wrna.70025","DOIUrl":"10.1002/wrna.70025","url":null,"abstract":"<p><p>Translation reprogramming-induced dysregulation of protein synthesis is a widespread phenomenon in disease progression, especially in tumor cells, where there is abnormally active protein synthesis to support the increasing demands of oncogene expression. This aberrant translation process contributes to various malignant phenotypes of tumors. In the process of protein synthesis, transfer RNAs (tRNAs) transport amino acids to the ribosome according to the codon sequence on mRNA to synthesize the corresponding peptide chain. Thus, tRNAs play a major role in the regulation of translation reprogramming. With the development of sequencing and mass spectrometry technologies, various modifications have been identified in tRNAs. Abnormal tRNA modifications lead to translation reprogramming by affecting the abundance of tRNAs, the cleavage of tRNAs, and the ability of tRNAs to decode mRNAs, thereby promoting the progression of tumors. This review focuses on the mechanisms by which aberrant tRNA modifications contribute to tumorigenesis through translation reprogramming, and provides a comprehensive summary and discussion on the clinical prospects of targeting excessive translation driven by tRNA modifications for cancer therapy. This article is categorized under: Translation > Mechanisms RNA Processing > RNA Editing and Modification.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70025"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875474","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":"G-Quadruplexes in Gene Regulation and Cellular Function.","authors":"Qi Wen, Lijin Guo, Farhad Bordbar, Qinghua Nie","doi":"10.1002/wrna.70019","DOIUrl":"10.1002/wrna.70019","url":null,"abstract":"<p><p>G-quadruplexes (G4s) are distinct nucleic acid secondary structures formed by guanine-rich sequences in both DNA and RNA. These structures readily form and fulfill diverse biological functions. The structural diversity of G4s is influenced by several factors, including their strand orientation, glycosidic bond angles, and loop configurations. G4s are widely distributed in functionally significant genomic regions, including telomeres, promoter regions, exons, 5' untranslated region (5' UTR), intron region, and 3' untranslated region (3' UTR). G4s are implicated in critical biological processes, including telomere elongation, DNA replication, DNA damage repair, transcription, translation, and epigenetic regulation. This overview offers a comprehensive analysis of the determinants of G4 structure and their impact on associated biological processes. Briefly, it describes the effects of G4s on cancers, viruses, and other pathogenic substances. This overview aims to contribute new ideas for the regulation of related mechanisms and their potential impact on the treatment strategies of related diseases. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70019"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627281","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":"From Junk DNA to Genomic Treasure: Impacts of Transposable Element DNA, RNA, and Protein in Mammalian Development and Disease.","authors":"Ten D Li, Katelyn Toohill, Andrew J Modzelewski","doi":"10.1002/wrna.70022","DOIUrl":"10.1002/wrna.70022","url":null,"abstract":"<p><p>Transposable elements (TEs) have hijacked cellular machineries to replicate and spread throughout host genomes. TEs now make up a significant portion of eukaryotic genomes and play notable roles in genomic evolution, driving both speciation and providing raw material for genetic innovation. Barbara McClintock's pioneering work on these \"jumping genes\" laid the foundation for modern TE research; however, her paradigm-shifting theories in which TEs act as \"controlling elements\" were initially rejected due to the long-held belief that TEs were \"junk\" or parasitic DNA elements. Historically, the highly repetitive nature of TEs made it challenging to both identify and investigate functions. However, recent advances in genomics have greatly accelerated our understanding of TEs. Despite their potential to cause insertional mutagenesis and disease, many transposable elements have been co-opted by host genomes to contribute to gene regulation and development. In contrast to protein-coding genes that typically begin their journey as DNA, are transcribed into RNA, and reach their ultimate functional form as proteins, TEs can function as cis-regulatory DNA, functional RNA, and in rare cases, domesticated proteins and fusion events between TE and host genes. Driven by rapidly advancing technologies, the roles of TEs in both development and disease are being uncovered faster than ever, making current and future work an exciting continuation of Barbara McClintock's groundbreaking legacy.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70022"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849262","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":"Role of the U1 snRNP Complex in Human Health and Disease.","authors":"Ericks S Soares, Caio Bruno Q S Leal, Vanessa V C Sinatti, Rafael M Bottós, Camila G M Zimmer","doi":"10.1002/wrna.70026","DOIUrl":"10.1002/wrna.70026","url":null,"abstract":"<p><p>The U1 small nuclear ribonucleoprotein (snRNP) complex is crucial for pre-mRNA splicing and the regulation of gene expression. As a core component of the spliceosome, it is responsible for recognizing 5'-splice sites and initiating the splicing process. Each subunit of this complex performs specific functions in the assembly and stabilization of the spliceosomal machinery. In addition to its classical role in splicing, the U1 snRNP complex is also involved in telescripting, a process that prevents premature polyadenylation. Dysregulation of U1 snRNP components has been associated with various disorders, including neurodegeneration, cancer, and autoimmune and eye diseases. Understanding the precise mechanisms of U1 snRNP complex dysregulation provides valuable insights into the molecular basis of these diseases, offering potential pathways for therapeutic intervention and prevention. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Mechanisms.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70026"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883860","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":"Alternative Splicing of Exon 23a in Neurofibromatosis Type 1 Pre-mRNA: Its Contribution to the Protein Structure and Function of Neurofibromin.","authors":"Annabelle G Elsner Pacheco, Hua Lou","doi":"10.1002/wrna.70021","DOIUrl":"10.1002/wrna.70021","url":null,"abstract":"<p><p>The neurofibromatosis type 1 (NF1) gene has 61 exons. The major alternative exon in NF1 pre-mRNA is exon 23a. Skipping and inclusion of this exon produce isoform I and isoform II neurofibromin, respectively. When the alternative exon was discovered in 1993, several experiments conducted in yeast and human cell lines quickly led to the conclusion that inclusion of this exon reduced the RasGAP function of the neurofibromin protein by 5-10-fold. Since then, research efforts on this seemingly important alternative splicing event have been sporadic, leaving many important questions unanswered, until after 2020 when several important papers related to the structure and function of exon 23a have been published. Two major advancements have been made. First, the cryo-EM structures of the full-length neurofibromin, of both isoforms, have been solved. More excitingly, the structure of isoform II neurofibromin that includes exon 23a provides important insight into why this isoform has reduced RasGAP activity. Second, the role of the altered splicing pattern of exon 23a in the development of high-grade glioma (HGG) has been investigated. In this review, we start with the introduction of alternative splicing of exon 23a, its discovery, differential expression patterns, and regulatory mechanisms that control this alternative splicing event. Next, we discuss the structural differences between the two isoforms which give insight into the differing RasGAP activities. We then review the in vivo biological function of the regulated inclusion of exon 23a, focusing on cognitive behaviors and brain tumor development. Finally, we briefly discuss the future directions of studies on NF1 exon 23a. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70021"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856563","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":"Unraveling the Role of Topoisomerase 3β (TOP3B) in mRNA Translation and Human Disease.","authors":"Julia E Warrick, Michael G Kearse","doi":"10.1002/wrna.70020","DOIUrl":"10.1002/wrna.70020","url":null,"abstract":"<p><p>mRNA translation is a highly orchestrated process that requires spatiotemporal control to ensure each protein is synthesized at the correct abundance, time, and location during human development and physiology. Classically, trans-acting RNA-binding proteins (RBPs) recognize cis-elements within mRNAs to provide one layer of gene-specific translational control. The function and properties of RBPs are diverse, with some harboring enzymatic capabilities, and can be multifaceted if present in larger RBP complexes. In this review, we focus on the role of Topoisomerase 3β (TOP3B) as a non-canonical RBP that is believed to influence the translation of select mRNAs and its connection with multiple human neurological disorders. Unlike any other encoded topoisomerase in the human genome, TOP3B is an mRNA-binding protein, catalytically favors RNA over DNA, and primarily localizes to the cytoplasm. Here we highlight important aspects of TOP3B as an RBP and raise multiple key questions for the field as a roadmap to better define its function in translational control and neuropathology. This article is categorized under: Translation > Regulation RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 4","pages":"e70020"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776323","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":"Alternative Splicing and CaV-Associated Channelopathies.","authors":"Willy Munyao, Md Mostafizur Rahman, Samuel A Sabzanov, Elizabeth H Chu, Ruizhi Wang, Zhifei Wang, Yong Yu, Matteo Ruggiu","doi":"10.1002/wrna.70016","DOIUrl":"10.1002/wrna.70016","url":null,"abstract":"<p><p>Voltage-gated calcium channels (VGCCs) are multi-subunit ion channel proteins that control and regulate a wide array of physiological processes. Their dysfunction has been implicated in several neurological, cardiac, psychiatric, endocrine, oncogenic, and muscular disorders. The diverse and specialized cellular functions involving VGCC-mediated calcium signaling stem from two primary mechanisms: differential and cell-specific expression of pore-forming (α1) and auxiliary subunit genes, and extensive alternative splicing of their pre-mRNA. All the 10 α1-encoding genes undergo alternative splicing to generate a wide array of cell-specific CaV variants with distinct biophysical, pharmacological, and protein-protein interaction properties. This proteomic diversity and the associated cell-specific expression signature of CaV splice variants are tightly regulated by trans-acting splicing factors-RNA-binding proteins that control the inclusion or skipping of alternatively spliced exons during post-transcriptional pre-mRNA processing. The discovery that several channelopathies are caused by aberrant splicing due to genetic mutations in either cis-acting binding elements on the pre-mRNA or in core splicing machinery components highlights the crucial role of alternative splicing in VGCC-related pathologies. These insights have opened new therapeutic avenues, as targeting the alternative splicing of disease-associated specific exons has recently emerged as a novel, promising treatment for neurodevelopmental disorders and channelopathies associated with splicing dysfunction.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 3","pages":"e70016"},"PeriodicalIF":6.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259041","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}