Carly L Lancaster, Kenneth H Moberg, Anita H Corbett
{"title":"Post-Transcriptional Regulation of Gene Expression and the Intricate Life of Eukaryotic mRNAs.","authors":"Carly L Lancaster, Kenneth H Moberg, Anita H Corbett","doi":"10.1002/wrna.70007","DOIUrl":"10.1002/wrna.70007","url":null,"abstract":"<p><p>In recent years, there has been a growing appreciation for how regulatory events that occur either co- or post-transcriptionally contribute to the control of gene expression. Messenger RNAs (mRNAs) are extensively regulated throughout their metabolism in a precise spatiotemporal manner that requires sophisticated molecular mechanisms for cell-type-specific gene expression, which dictates cell function. Moreover, dysfunction at any of these steps can result in a variety of human diseases, including cancers, muscular atrophies, and neurological diseases. This review summarizes the steps of the central dogma of molecular biology, focusing on the post-transcriptional regulation of gene expression.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70007"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587421","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}
Dezhi Yan, Qingliu He, Chunjian Wang, Tian Li, Xueping Yi, Haisheng Yu, Wenfei Wu, Hanyun Yang, Wenzhao Wang, Liang Ma
{"title":"miR-135b: A Potential Biomarker for Pathological Diagnosis and Biological Therapy.","authors":"Dezhi Yan, Qingliu He, Chunjian Wang, Tian Li, Xueping Yi, Haisheng Yu, Wenfei Wu, Hanyun Yang, Wenzhao Wang, Liang Ma","doi":"10.1002/wrna.70002","DOIUrl":"10.1002/wrna.70002","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs found in eukaryotes with post-transcriptional regulatory functions. A variety of miRNAs is differentially expressed in cancer tissues and thus can be used as biomarkers. microRNA-135b-5p (miR-135b) has been shown to be involved in the pathological processes of a variety of neoplastic and non-neoplastic diseases. Under different conditions, miR-135b has different tumor suppressive and carcinogenic effects. miR-135b regulates the development of cancer, including metabolism, proliferation, apoptosis, invasion, fibrosis, angiogenesis, immunomodulation, and drug resistance. miR-135b can be used as a new biomarker for tumor diagnosis and prognosis, which has the potential for clinical guidance. This article reviews the relevant research on miR-135B in the field of tumors, including the biogenesis background of miR-135b, the expression of miR-135b in tumors, and the related targets and signaling pathways of miR-135b mediating tumor progression in order to sort out and explore the clinical transformation value of miR-135b.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70002"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543773","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}
Ruixuan Zhu, Zixin Pi, Yaqian Shi, Yangfan Xiao, Rong Xiao
{"title":"The Role of Non-Coding RNA in Systemic Sclerosis: From Mechanism to Translation.","authors":"Ruixuan Zhu, Zixin Pi, Yaqian Shi, Yangfan Xiao, Rong Xiao","doi":"10.1002/wrna.70003","DOIUrl":"10.1002/wrna.70003","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by imbalanced immunity, vasculopathy, and excessive fibrosis. The etiology and pathology of this disease remain to be fully elucidated. Genetic predisposition, along with epigenetic modifications are widely considered to significantly affect its development. Among the components of epigenetics, non-coding RNAs (ncRNAs), comprising various types such as microRNA, long ncRNA, circular RNA, and others, play a crucial role. These ncRNAs perform several functions in the development of SSc and can potentially be employed as new targets for its diagnosis and treatment. This review discusses the roles of ncRNAs in the three primary pathological hallmarks-vasculopathy, imbalanced immunity, and excessive fibrosis-of SSc and highlights research progress in the role of RNAs in translational medicine against SSc. The review also provides a comprehensive outline of the key function of ncRNAs in SSc.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70003"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568347","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}
Encarnacion Martinez-Salas, Salvador Abellan, Rosario Francisco-Velilla
{"title":"Understanding GEMIN5 Interactions: From Structural and Functional Insights to Selective Translation.","authors":"Encarnacion Martinez-Salas, Salvador Abellan, Rosario Francisco-Velilla","doi":"10.1002/wrna.70008","DOIUrl":"10.1002/wrna.70008","url":null,"abstract":"<p><p>GEMIN5 is a predominantly cytoplasmic protein, initially identified as a member of the survival of motor neurons (SMN) complex. In addition, this abundant protein modulates diverse aspects of RNA-dependent processes, executing its functions through the formation of multi-component complexes. The modular organization of structural domains present in GEMIN5 enables this protein to perform various functions through its interaction with distinct partners. The protein is responsible for the recognition of small nuclear (sn)RNAs through its N-terminal region, and therefore for snRNP assembly. Beyond its role in spliceosome assembly, GEMIN5 regulates translation through the interaction with either RNAs or proteins. In the central region, a robust dimerization domain acts as a hub for protein-protein interaction, while a non-canonical RNA-binding site is located towards the C-terminus. Interestingly, GEMIN5 regulates the partitioning of mRNAs into polysomes, likely due to its RNA-binding capacity and its ability to bind native ribosomes. Understanding the functional and structural organization of the protein has brought an increasing interest in the last years with important implications in human disease. Patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. This review discusses recent relevant works aimed at understanding the molecular mechanisms of GEMIN5 activity in gene expression, and also the challenges to discover new functions.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70008"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773637","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}
Moh Egy Rahman Firdaus, Eliana Dukhno, Rupali Kapoor, Piotr Gerlach
{"title":"Two Birds With One Stone: RNA Virus Strategies to Manipulate G3BP1 and Other Stress Granule Components.","authors":"Moh Egy Rahman Firdaus, Eliana Dukhno, Rupali Kapoor, Piotr Gerlach","doi":"10.1002/wrna.70005","DOIUrl":"10.1002/wrna.70005","url":null,"abstract":"<p><p>Stress granules (SGs) are membrane-less organelles forming in the cytoplasm in response to various types of stress, including viral infection. SGs and SG-associated proteins can play either a proviral role, by facilitating viral replication, or an antiviral role, by limiting the translation capacity, sequestering viral RNA, or contributing to the innate immune response of the cell. Consequently, viruses frequently target stress granules while counteracting cellular translation shut-off and the antiviral response. One strategy is to sequester SG components, not only to impair their assembly but also to repurpose and incorporate them into viral replication sites. G3BP1 is a key SG protein, driving its nucleation through protein-protein and protein-RNA interactions. Many cellular proteins, including other SG components, interact with G3BP1 via their ΦxFG motifs. Notably, SARS-CoV N proteins and alphaviral nsP3 proteins contain similar motifs, allowing them to compete for G3BP1. Several SG proteins have been shown to interact with the flaviviral capsid protein, which is primarily responsible for anchoring the viral genome inside the virion. There are also numerous examples of structured elements within coronaviral and flaviviral RNAs recruiting or sponging SG proteins. Despite these insights, the structural and biochemical details of SG-virus interactions remain largely unexplored and are known only for a handful of cases. Exploring their molecular relevance for infection and discovering new examples of direct SG-virus contacts is highly important, as advances in this area will open new possibilities for the design of targeted therapies and potentially broad-spectrum antivirals.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70005"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765260","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":"Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation.","authors":"Sherif Rashad, Aseel Marahleh","doi":"10.1002/wrna.70011","DOIUrl":"10.1002/wrna.70011","url":null,"abstract":"<p><p>Transfer RNA (tRNA) is not merely a passive carrier of amino acids, but an active regulator of mRNA translation controlling codon bias and optimality. The synthesis of various tRNA modifications is regulated by many \"writer\" enzymes, which utilize substrates from metabolic pathways or dietary sources. Metabolic and bioenergetic pathways, such as one-carbon (1C) metabolism and the tricarboxylic acid (TCA) cycle produce essential substrates for tRNA modifications synthesis, such as S-Adenosyl methionine (SAM), sulfur species, and α-ketoglutarate (α-KG). The activity of these metabolic pathways can directly impact codon decoding and translation via regulating tRNA modifications levels. In this review, we discuss the complex interactions between diet, metabolism, tRNA modifications, and mRNA translation. We discuss how nutrient availability, bioenergetics, and intermediates of metabolic pathways, modulate the tRNA modification landscape to fine-tune protein synthesis. Moreover, we highlight how dysregulation of these metabolic-tRNA interactions contributes to disease pathogenesis, including cancer, metabolic disorders, and neurodegenerative diseases. We also discuss the new emerging field of GlycoRNA biology drawing parallels from glycobiology and metabolic diseases to guide future directions in this area. Throughout our discussion, we highlight the links between specific modifications, their metabolic/dietary precursors, and various diseases, emphasizing the importance of a metabolism-centric tRNA view in understanding many pathologies. Future research should focus on uncovering the interplay between metabolism and tRNA in specific cellular and disease contexts. Addressing these gaps will guide new research into novel disease interventions.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70011"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677347","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}
Bence György Gombás, Orsolya Németh-Szatmári, Bence Nagy-Mikó, Zoltán Villányi
{"title":"Role of Assemblysomes in Cellular Stress Responses.","authors":"Bence György Gombás, Orsolya Németh-Szatmári, Bence Nagy-Mikó, Zoltán Villányi","doi":"10.1002/wrna.70009","DOIUrl":"10.1002/wrna.70009","url":null,"abstract":"<p><p>Assemblysomes are recently discovered intracellular RNA-protein complexes that play important roles in cellular stress response, regulation of gene expression, and also in co-translational protein assembly. In this review, a wide spectrum overview of assemblysomes is provided, including their discovery, mechanism of action, characteristics, and potential applications in several fields. Assemblysomes are distinct liquid-liquid phase-separated condensates; they have certain unique properties differentiating them from other cellular granules. They are composed of ribosome-nascent protein chain complexes and are resistant to cycloheximide and EDTA. The discovery and observation of intracellular condensates, like assemblysomes, have further expanded our knowledge of cellular stress response mechanisms, particularly in DNA repair processes and defense against proteotoxicity. Ribosome profiling experiments and next-generation sequencing of cDNA libraries extracted from EDTA-resistant pellets-of ultracentrifuged cell lysates-have shed light on the composition and dynamics of assemblysomes, revealing their role as repositories for pre-made stress-responsive ribosome-nascent chain complexes. This review gives an exploration of assemblysomes' potential clinical applications from multiple aspects, including their usefulness as diagnostic biomarkers for chemotherapy resistance and their implications in cancer therapy. In addition, in this overview, we raise some theoretical ideas of industrial and agricultural applications connected to these membraneless organelles. However, we see several challenges. On one hand, we need to understand the complexity of assemblysomes' multiple functions and regulations; on the other hand, it is essential to bridge the gap between fundamental research and practical applications. Overall, assemblysome research can be perceived as a promising upcomer in the improvement of biomedical settings as well as those connected to agricultural and industrial aspects.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70009"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664710","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":"Intron-Derived Lariat RNAs Go Stable.","authors":"Dan Liao, Binglian Zheng","doi":"10.1002/wrna.70006","DOIUrl":"10.1002/wrna.70006","url":null,"abstract":"<p><p>During pre-mRNA splicing, introns are removed by the spliceosome, and the flanking exons are ligated to form mature mRNA, which is subsequently translated into protein. Traditionally, intronic RNAs have been regarded as \"junk\", presumed to be degraded for nucleotide turnover. Notably, after debranching, some linearized lariat RNAs can be further processed into snoRNAs, miRNAs, and other long non-coding RNAs. However, recent studies have shown that many intron-derived lariat RNAs can escape degradation and remain stable across various eukaryotic organisms, indicating they may play significant roles in cellular processes. Moreover, these naturally retained lariat RNAs are frequently observed in circular forms in vivo, suggesting that their linear tails are highly susceptible to degradation. This highlights lariat RNAs as an important source of circular RNAs. Furthermore, many lariat-derived circRNAs have been detected in the cytoplasm, implying active nuclear export and potential roles in cytoplasmic processes. In this review, we provide an overview of the life cycle of intron-derived lariat RNAs, focusing on their biogenesis, degradation, and retention. We also discuss the mechanisms that enable their resistance to degradation and the biological functions of stable lariat RNAs, shedding light on these seemingly \"nonsense\" yet inevitably produced non-coding intronic RNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70006"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543753","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":"Functional Landscape of hnRNPA3 in Disease Pathogenesis.","authors":"Fang Chen, Genghan Li, Shuang Fu, Jihong Zhang","doi":"10.1002/wrna.70010","DOIUrl":"10.1002/wrna.70010","url":null,"abstract":"<p><p>The heterogeneous nuclear ribonucleic acid protein family participates in various intracellular reactions, such as RNA splicing, transport, DNA repair, cellular signal transduction, and gene expression regulation, and is involved in various disease processes. As a late-discovered member, heterogeneous nuclear ribonucleoprotein A3 has received increasing attention, but its main physiological functions and exact mechanisms involved in disease processes have not yet reached a consensus. In this review, we summarize the function of heterogeneous nuclear ribonucleoprotein A3 and the literature on its role in neurodegenerative and metabolic diseases, as well as in various tumors, to explore the applicability of heterogeneous nuclear ribonucleoprotein A3 as a therapeutic target and prognostic indicator.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 2","pages":"e70010"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700978","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}
Syed Wasifa Qadri, Nisa Manzoor Shah, Ravi S Muddashetty
{"title":"Epitranscriptome-Mediated Regulation of Neuronal Translation.","authors":"Syed Wasifa Qadri, Nisa Manzoor Shah, Ravi S Muddashetty","doi":"10.1002/wrna.70004","DOIUrl":"10.1002/wrna.70004","url":null,"abstract":"<p><p>Epitranscriptomic modification of RNA is an important layer of regulation for gene expression. RNA modifications come in many flavors and generate a complex tapestry of a regulatory network. Here, we focus on two major RNA modifications, one on rRNA (2'O Methylation) and another on mRNA (N<sup>6</sup>-Methyladenosine [m<sup>6</sup>A]) and their impact on translation. The 2'O methyl group addition on the ribose sugar of rRNA plays a critical role in RNA folding, ribosome assembly, and its interaction with many RNA binding proteins. Differential methylation of these sites contributes to ribosome heterogeneity and generates potential \"specialized ribosomes.\" Specialized ribosomes are proposed to play a variety of important roles in maintaining pluripotency, lineage specification, and compartmentalized and activity-mediated translation in neurons. The m<sup>6</sup>A modification, on the other hand, determines the stability, transport, and translation of subclasses of mRNA. The dynamic nature of m<sup>6</sup>A owing to the localization and activity of its writers, readers, and erasers makes it a powerful tool for spatiotemporal regulation of translation. While substantial information has accumulated on the nature and abundance of these modifications, their functional consequences are still understudied. In this article, we review the literature constructing the body of our understanding of these two modifications and their outcome on the regulation of translation in general and their impact on the nervous system in particular. We also explore the possibility of how these modifications may collaborate in modulating translation and provoke the thought to integrate the functions of multiple epitranscriptome modifications.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 1","pages":"e70004"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441426","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}