Wiley Interdisciplinary Reviews: RNA最新文献

Decoding the ncRNA Script: Elucidation of Major Host Regulatory lncRNAs and circRNAs Shaping RNA Virus Pathogenesis. 解码ncRNA脚本：主要宿主调控lncrna和circrna塑造RNA病毒发病机制的阐明。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70064

Souhardya Saha, Rimbik Chatterjee, Suvrotoa Mitra, Doyel Biswas, Shin-Ichi Miyoshi, Daisuke Imamura, Mamta Chawla-Sarkar

{"title":"Decoding the ncRNA Script: Elucidation of Major Host Regulatory lncRNAs and circRNAs Shaping RNA Virus Pathogenesis.","authors":"Souhardya Saha, Rimbik Chatterjee, Suvrotoa Mitra, Doyel Biswas, Shin-Ichi Miyoshi, Daisuke Imamura, Mamta Chawla-Sarkar","doi":"10.1002/wrna.70064","DOIUrl":"https://doi.org/10.1002/wrna.70064","url":null,"abstract":"Viruses are key infectious agents causing large-scale mortality among humans every year with the recent example of the devastating COVID-19 pandemic. RNA viruses are often associated with higher pathogenicity and their molecular mechanisms of entry into host cells, replication, transmission, and propagation remain poorly understood. To facilitate virus replication and propagation, these viruses regulate the host gene transcription and translation, key cellular processes like apoptosis, autophagy, innate as well as adaptive immune responses, lipid biosynthesis, and other key host signaling processes. They hijack and exploit the host cell machinery by modulating the expression of host proteins and ncRNAs. Some of the regulatory RNAs that these viruses modulate involve lncRNAs, circRNAs and ceRNA networks. RNA viruses alter or control key cellular processes of these RNAs by directly or indirectly interacting with both host and viral proteins and other non-coding RNAs. Through the alteration of regulation of non-coding RNAs, the viruses have been demonstrated to alter several biological processes primarily metabolic pathways, inflammation, and immune pathways like interferon signaling and other innate immune pathways to aid virus replication, pathogenesis and immune evasion. These differentially expressed regulatory RNAs can be further studied to develop potential antiviral therapeutics and vaccines. CeRNA networks involve the role of protein-coding mRNAs and competing ncRNAs like lncRNA, miRNA, and circRNA. This review explores some of the reported modulations of host lncRNAs, circRNAs, and ceRNA networks in RNA virus infections to understand their importance and role in virus pathogenesis.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70064"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196982","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}

引用次数: 0

The Hypothesis-Driven Loop: An Integrated Dry-Wet Framework for Long Noncoding RNA Functional Analysis. 假设驱动环：长链非编码RNA功能分析的干湿集成框架。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70059

Hidenori Tani

{"title":"The Hypothesis-Driven Loop: An Integrated Dry-Wet Framework for Long Noncoding RNA Functional Analysis.","authors":"Hidenori Tani","doi":"10.1002/wrna.70059","DOIUrl":"https://doi.org/10.1002/wrna.70059","url":null,"abstract":"Only a small minority of annotated long noncoding RNAs (lncRNAs) have a molecular function established by direct experiment, and the gap widens with every new catalog. Existing reviews catalog methods thoroughly but rarely formalize how negative or discordant wet-laboratory results should feed back into computational prioritization, so the iterative refinement that lncRNA biology requires is left implicit. We set out the Hypothesis-Driven Loop, which recasts lncRNA functional analysis as a cycle of three phases: Generation (computational priors), Testing (wet validation), and Refinement (integration that updates the priors for the next round). The cycle itself is Platt's strong inference; what is specific to lncRNAs are the constraints that reshape it-a detectability floor that gates every functional claim, an orders-of-magnitude asymmetry between prediction and validation throughput, and the ambiguity of what a locus-level perturbation actually removes-together with the deliverable each phase must produce. We map existing tools onto the appropriate phase; give a one-page Loop worksheet with an odds-form procedure for updating priors and pre-declared stopping boundaries; and specify how a negative result is triaged as technical or biological before it may revise a hypothesis. Three worked programs-BRIC-seq and the SLiTs paradigm from our laboratory, and HOTAIR, assembled by independent groups from results that disagreed-show that Loops can be entered at different phases and that closure can be a community-level property. The claim is deliberately narrow: iterative dry-wet coupling, recorded so that it can be audited, is one discipline that may help narrow the annotation-function gap.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70059"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115641","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}

引用次数: 0

Experimental and Computational Tools for Mapping Circular RNA Modifications. 绘制环状RNA修饰的实验和计算工具。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70055

Gaurahari Sahoo, Dishanee Santra, Amaresh Chandra Panda

{"title":"Experimental and Computational Tools for Mapping Circular RNA Modifications.","authors":"Gaurahari Sahoo, Dishanee Santra, Amaresh Chandra Panda","doi":"10.1002/wrna.70055","DOIUrl":"10.1002/wrna.70055","url":null,"abstract":"Posttranscriptional RNA modifications and their impact on the structure and function have been extensively studied on linear RNAs. As RNA modifications affect RNA structure, stability, localization, and translation, several methods have been developed to study modifications on linear RNAs. These modifications on RNAs ultimately regulate gene expression. One of the poorly characterized classes of RNA critical for gene expression is circular RNAs (circRNAs), which are ubiquitously expressed and are covalently closed RNA molecules. Although advances in sequencing technologies have greatly enhanced the identification of RNA modifications and their importance in gene regulation, the effects of these modifications on circRNA structure and function are only now emerging. Only a few modifications, like N6-methyladenosine (m6A), 5-methylcytosine (m5C), adenosine-to-inosine (A-to-I), and to a lesser extent N1-methyladenosine (m1A), have been reported so far for circRNAs. In this article, we discuss the importance of these modifications and their implications in circRNA function. Moreover, we will discuss molecular and computational methods for detecting circRNA modifications, to help researchers studying circRNAs select the most effective methods for investigating modifications in this novel class of circRNAs.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70055"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901037","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}

引用次数: 0

Machine Learning to Enhance Biophysical Models for Riboswitch Discovery. 机器学习增强核糖开关发现的生物物理模型。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70062

Rami Zakh, Alexander Churkin, Ahmed Elbanna, Sumit Mukherjee, Danny Barash

{"title":"Machine Learning to Enhance Biophysical Models for Riboswitch Discovery.","authors":"Rami Zakh, Alexander Churkin, Ahmed Elbanna, Sumit Mukherjee, Danny Barash","doi":"10.1002/wrna.70062","DOIUrl":"https://doi.org/10.1002/wrna.70062","url":null,"abstract":"Riboswitches are RNA-based genetic control elements that provide a unique mechanism of gene regulation. They function without the participation of proteins and are believed to represent ancient regulatory systems on the evolutionary timescale. To expand the search for novel riboswitches of significant interest, such as eukaryotic riboswitches beyond the purine riboswitch class, the integration of machine learning into RNA design offers considerable potential to improve the effectiveness of traditional search methods. Many riboswitch aptamers that could be targeted in such searches are larger than purine riboswitch aptamers, making their design time-consuming (e.g., SAM, lysine, FMN, glycine, and cobalamin riboswitches). In an example problem unrelated to the discovery of novel riboswitches, namely challenges in the eteRNA game, it has been shown that a transformer encoder-decoder model is effective in solving difficult inverse RNA folding challenges. In the outlined approach, machine learning is used as a preprocessing step before RNA design, rather than relying on random inputs to the Monte Carlo method, and the RNA design step crucially depends on a biophysical model for the forward problem of RNA folding prediction. It is therefore suggested to optimize the training of the machine learning model and then utilize this approach for riboswitch discovery to make searches for riboswitches larger than purine aptamers more efficient and robust.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70062"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115654","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}

引用次数: 0

RNA-Protein Assemblies: A Review of Biophysical Principles and Coarse-Grained Modeling Approaches. rna -蛋白质组装：生物物理原理和粗粒度建模方法综述。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70061

Muhammad Waleed Iqbal, Patrick R Onck

{"title":"RNA-Protein Assemblies: A Review of Biophysical Principles and Coarse-Grained Modeling Approaches.","authors":"Muhammad Waleed Iqbal, Patrick R Onck","doi":"10.1002/wrna.70061","DOIUrl":"https://doi.org/10.1002/wrna.70061","url":null,"abstract":"RNA-protein assemblies are fundamental organizers of eukaryotic cell biology, participating in diverse processes such as ribosome biogenesis in nucleoli, mRNA sequestration in nuclear speckles, and genome packaging in viral ribonucleoprotein (vRNP) complexes. Across these systems, multivalent RNA-protein interactions promote self-organization, contributing directly to liquid-liquid phase separation (LLPS) in nucleoli and nuclear speckles, while facilitating assembly and intermediate states in mature structurally organized vRNPs. This review critically examines the molecular grammar underlying these three paradigmatic systems, focusing on how sequence-encoded RNA-IDR chemistry determines condensate morphology, compositional selectivity, and material properties. We then evaluate the experimental and computational approaches used to characterize RNA-protein assemblies, with particular focus on coarse-grained (CG) forcefield development across HPS, Mpipi, CALVADOS, and 1BPA families. We also discuss how emerging multi-domain protein (MDP) models and RNA-compatible forcefields are optimizing the predictive accuracy of molecular simulations. Finally, we explore physics-based and data-driven predictors of LLPS, and reiterate the need for a framework that can predict sequence-based heterotypic IDR-RNA co-phase separation.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70061"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115674","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}

引用次数: 0

RNA-Protein Reciprocity and the Limits of RBP Buffering. rna -蛋白互易性和RBP缓冲的极限。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70065

Epaminondas Doxakis

{"title":"RNA-Protein Reciprocity and the Limits of RBP Buffering.","authors":"Epaminondas Doxakis","doi":"10.1002/wrna.70065","DOIUrl":"10.1002/wrna.70065","url":null,"abstract":"RNA-binding proteins (RBPs) regulate RNA processing, localization, translation, and decay, yet similar perturbations can have different consequences across cells and tissues. RNA-protein reciprocity relates this variation to the balance between the binding sites presented by RNA and the protein available to regulate them. Regulation can remain stable while sufficient RBP is available, but become sensitive to small changes as that reserve narrows. The biological consequence depends on which transcripts lose regulation and how strongly the cell depends on their products. Examples from endogenous regulatory RNAs, repeat-expansion diseases, viral infection, and cancer show that RNA-dependent RBP redistribution can preserve cellular function or contribute to its failure. Binding affinity, partner proteins, autoregulation, and RNA-dependent assembly shape these responses. This Perspective develops the framework and proposes experiments to connect changes in local RNA demand and RBP supply with target binding and biological output. The aim is to identify when a modest molecular perturbation has a disproportionate functional effect, and when restoring the RNA-protein balance can recover regulation.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70065"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207930","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}

引用次数: 0

Impact of the Diversity in the 5' UTR on Translation Regulation. 5' UTR的多样性对翻译监管的影响。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70060

Giulia Cardamone, Melanie Flohr, Irina Bode, Tobias Schmid

{"title":"Impact of the Diversity in the 5' UTR on Translation Regulation.","authors":"Giulia Cardamone, Melanie Flohr, Irina Bode, Tobias Schmid","doi":"10.1002/wrna.70060","DOIUrl":"https://doi.org/10.1002/wrna.70060","url":null,"abstract":"The 5' untranslated region (UTR) of mRNAs is crucial to regulate translation initiation. Diversity in the 5' UTR can be created by alternative transcription start site (TSS) selection and alternative splicing. Alternative TSS directly impact the first exon length or alternative first exon usage, while alternative splicing further contributes to generating different 5' UTR isoforms by for example, cassette exons inclusion, intron retention, and alternative 5' or 3' splice sites. Alternative TSS and alternative splicing in the 5' UTR directly affect translation efficiency by generating different isoforms that may include or exclude regulatory sequence elements and secondary structures in the 5' UTR. Among the regulatory elements, 5' UTRs may harbor translation-inhibitory upstream open reading frames (uORFs) as well as internal ribosome entry sites (IRESs), which are able to recruit the ribosome in a cap-independent manner. Both uORF- and IRES-mediated mechanisms contribute to target-specific protein production, especially under stress conditions associated with an inhibition of global translation. Mechanisms generating different 5' UTR isoforms therefore represent an additional sophisticated layer to regulate transcript-selective translation efficiency.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70060"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115614","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}

引用次数: 0

Viroid-Derived siRNAs: Minimal RNAs Driving Multiscale Perturbations of Host Regulatory Systems. 类病毒衍生的sirna：驱动宿主调控系统多尺度扰动的最小rna。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70058

Katia Aviña-Padilla, Ana Belén Mendoza-Soto, Yocssiry Elena Ochoa-Rodríguez, Flor Citlally Alcántar-Aguirre, Loranda Calderón-Zamora

{"title":"Viroid-Derived siRNAs: Minimal RNAs Driving Multiscale Perturbations of Host Regulatory Systems.","authors":"Katia Aviña-Padilla, Ana Belén Mendoza-Soto, Yocssiry Elena Ochoa-Rodríguez, Flor Citlally Alcántar-Aguirre, Loranda Calderón-Zamora","doi":"10.1002/wrna.70058","DOIUrl":"10.1002/wrna.70058","url":null,"abstract":"Viroids are the simplest known infectious agents, consisting of noncoding circular RNAs that replicate autonomously in plant hosts while inducing profound and systemic alterations in host biology. This apparent paradox positions viroids as powerful models for understanding how RNA molecules encode biological information independently of protein translation. A hallmark of viroid infection is the production of viroid-derived small interfering RNAs (vd-siRNAs) by the host RNA silencing machinery. Here, we propose that vd-siRNAs function not merely as antiviroid byproducts, but as active effectors that translate RNA structural information into gene regulatory activity. Through sequence complementarity and selective incorporation into Argonaute complexes, vd-siRNAs influence host gene expression at multiple levels, including transcript abundance, protein accumulation, epigenetic states, and metabolic pathways. Importantly, their effects extend beyond individual targets and are consistent with broader perturbations of interconnected host regulatory networks, potentially contributing to coordinated transcriptional reprogramming and disease-associated phenotypes. By integrating molecular, transcriptomic, epigenetic, and systems-level evidence, we propose a \"structure-to-network\" perspective in which viroid RNAs function as minimal informational systems capable of interfacing with complex cellular pathways. Within this context, vd-siRNAs emerge as mechanistic links between RNA architecture and multiscale biological responses. Finally, we discuss how this framework expands our understanding of RNA-mediated regulation and highlights the broader regulatory potential of structured noncoding RNAs.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":"17 5","pages":"e70058"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169593","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}

引用次数: 0

Toward Mapping Spatiotemporally Resolved Transcriptomes and RNA-Protein Interactions. 定位时空分解转录组和rna -蛋白相互作用。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70057

Antto J Norppa, Minna-Liisa Änkö

引用次数: 0

Emerging Hallmarks of Functional Proteins Encoded by Non-Canonical ORFs. 非规范orf编码的功能蛋白的新特征。

IF 4.4 2区生物学

Wiley Interdisciplinary Reviews: RNA Pub Date : 2026-09-01 DOI: 10.1002/wrna.70063

Feng Zhou, Jiawen Jiang, Tianyu Lei, Yue Chang, Hong Zhang

引用次数: 0