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":"https://doi.org/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":"","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":"","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":"https://doi.org/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":"https://doi.org/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}
{"title":"Intron-Derived Lariat RNAs Go Stable.","authors":"Dan Liao, Binglian Zheng","doi":"10.1002/wrna.70006","DOIUrl":"https://doi.org/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}
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":"https://doi.org/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}
Katarzyna Grelewska-Nowotko, Ahmed Eisa Elhag, Tomasz Wojciech Turowski
{"title":"Transcription Kinetics in the Coronavirus Life Cycle.","authors":"Katarzyna Grelewska-Nowotko, Ahmed Eisa Elhag, Tomasz Wojciech Turowski","doi":"10.1002/wrna.70000","DOIUrl":"https://doi.org/10.1002/wrna.70000","url":null,"abstract":"<p><p>Coronaviruses utilize a positive-sense single-strand RNA, functioning simultaneously as mRNA and the genome. An RNA-dependent RNA polymerase (RdRP) plays a dual role in transcribing genes and replicating the genome, making RdRP a critical target in therapies against coronaviruses. This review explores recent advancements in understanding the coronavirus transcription machinery, discusses it within virus infection context, and incorporates kinetic considerations on RdRP activity. We also address steric limitations in coronavirus replication, particularly during early infection phases, and outline hypothesis regarding translation-transcription conflicts, postulating the existence of mechanisms that resolve these issues. In cells infected by coronaviruses, abundant structural proteins are synthesized from subgenomic RNA fragments (sgRNAs) produced via discontinuous transcription. During elongation, RdRP can skip large sections of the viral genome, resulting in the creation of shorter sgRNAs that reflects the stoichiometry of viral structural proteins. Although the precise mechanism of discontinuous transcription remains unknown, we discuss recent hypotheses involving long-distance RNA-RNA interactions, helicase-mediated RdRP backtracking, dissociation and reassociation of RdRP, and RdRP dimerization.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 1","pages":"e70000"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932892","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":"Hypothesis for Molecular Evolution in the Pre-Cellular Stage of the Origin of Life.","authors":"Yong Wang, Yiling Du","doi":"10.1002/wrna.70001","DOIUrl":"https://doi.org/10.1002/wrna.70001","url":null,"abstract":"<p><p>Life was originated from inorganic world and had experienced a long period of evolution in about 3.8 billion years. The time for emergence of the pioneer creations on Earth is debatable nowadays, and how the scenario for the prebiotic molecular interactions is still mysterious. Before the spreading of cellular organisms, chemical evolution was perhaps prevailing for millions of years, in which inorganic biosynthesis was ultimately replaced by biochemical reactions. Understanding the major molecular players and their interactions toward cellular life is fundamental for current medical science and extraterrestrial life exploration. In this review, we propose a road map for the primordial molecular evolution in early Earth, which probably occurred adjacent to hydrothermal vents with a strong gradient of organic molecules, temperature, and metal contents. Natural selection of the macromolecules with strong secondary structures and catalytic centers is associated with decreasing of overall entropy of the biopolymers. Our review may shed lights into the important selection of gene-coding RNA with secondary structures from large amounts of random biopolymers and formation of ancient ribosomes with biological machines supporting the basic life processes. Integration of the free environmental ribosomes by the early cellular life as symbiotic molecular machines is probably the earliest symbiosis on Earth.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"16 1","pages":"e70001"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012805","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}
Izabela Broniarek, Daria Niewiadomska, Krzysztof Sobczak
{"title":"Contribution of DNA/RNA Structures Formed by Expanded CGG/CCG Repeats Within the FMR1 Locus in the Pathogenesis of Fragile X-Associated Disorders.","authors":"Izabela Broniarek, Daria Niewiadomska, Krzysztof Sobczak","doi":"10.1002/wrna.1874","DOIUrl":"https://doi.org/10.1002/wrna.1874","url":null,"abstract":"<p><p>Repeat expansion disorders (REDs) encompass over 50 inherited neurological disorders and are characterized by the expansion of short tandem nucleotide repeats beyond a specific repeat length. Particularly intriguing among these are multiple fragile X-associated disorders (FXds), which arise from an expansion of CGG repeats in the 5' untranslated region of the FMR1 gene. Despite arising from repeat expansions in the same gene, the clinical manifestations of FXds vary widely, encompassing developmental delays, parkinsonism, dementia, and an increased risk of infertility. FXds also exhibit molecular mechanisms observed in other REDs, that is, gene- and protein-loss-of-function and RNA- and protein-gain-of-function. The heterogeneity of phenotypes and pathomechanisms in FXds results from the different lengths of the CGG tract. As the number of repeats increases, the structures formed by RNA and DNA fragments containing CGG repeats change significantly, contributing to the diversity of FXd phenotypes and mechanisms. In this review, we discuss the role of RNA and DNA structures formed by expanded CGG repeats in driving FXd pathogenesis and how the genetic instability of CGG repeats is mediated by the complex interplay between transcription, DNA replication, and repair. We also discuss therapeutic strategies, including small molecules, antisense oligonucleotides, and CRISPR-Cas systems, that target toxic RNA and DNA involved in the development of FXds.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1874"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629053","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":"The Unusual Role of Ribonuclease L in Innate Immunity.","authors":"Agnes Karasik, Nicholas R Guydosh","doi":"10.1002/wrna.1878","DOIUrl":"10.1002/wrna.1878","url":null,"abstract":"<p><p>Ribonuclease L is an endonuclease that is activated as part of the dsRNA-driven innate immune response. Active RNase L cleaves pathogenic RNAs as a way to eliminate infections. However, there are additional and unexpected ways that RNase L causes changes in the host that promote an immune response and contribute to its role in host defense. Central to these unconventional mechanisms is the observation that RNase L also degrades the mRNA of the host. In turn, mRNA fragments that RNase L generates can be translated. This causes activation of a ribosome collision sensor that leads to downstream signaling and cell death. Additionally, the liberation of RNA binding proteins after RNA decay appears to affect gene expression. In this review, we discuss these and other recent advances that focus on novel and unusual ways RNase L contributes to innate immunity.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1878"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898607","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":"Challenges in Therapeutically Targeting the RNA-Recognition Motif.","authors":"Stefan Schmeing, Peter 't Hart","doi":"10.1002/wrna.1877","DOIUrl":"10.1002/wrna.1877","url":null,"abstract":"<p><p>The RNA recognition motif (RRM) is the most common RNA binding domain found in the human proteome. RRM domains provide RNA-binding proteins with sequence specific RNA recognition allowing them to participate in RNA-centric processes such as mRNA maturation, translation initiation, splicing, and RNA degradation. They are drivers of various diseases through overexpression or mutation, making them attractive therapeutic targets and addressing these proteins through their RRM domains with chemical compounds is gaining ever more attention. However, it is still very challenging to find selective and potent RNA-competitors due to the small size of the domain and high structural conservation of its RNA binding interface. Despite these challenges, a selection of compounds has been reported for several RRM containing proteins, but often with limited biophysical evidence and low selectivity. A solution to selectively targeting RRM domains might be through avoiding the RNA-binding surface altogether, but rather look for composite pockets formed with other proteins or for protein-protein interaction sites that regulate the target's activity but are less conserved. Alternative modalities, such as oligonucleotides, peptides, and molecular glues, are exciting new approaches to address these challenging targets and achieve the goal of therapeutic intervention at the RNA regulatory level.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"15 6","pages":"e1877"},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819417","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}