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.
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.
Accurate removal of intervening intronic sequences from pre-mRNA is required for proper eukaryotic gene expression. This process, termed pre-mRNA splicing, is carried out by a spliceosome, a dynamic RNA-protein macromolecular machinery. Proteomic studies have shown that many spliceosomal components and associated factors harbor protein arginine methylation, a type of post-translational modification. These findings raise the question of how arginine methylation influences the process or outcome of pre-mRNA splicing. Although targeted studies have provided important molecular insights into how this modification regulates splicing protein subcellular localization, abundance, RNA/protein interactions, and snRNP biogenesis, much remains unknown, especially given the large number of methylated proteins identified that have known roles in regulating pre-mRNA splicing. In this review, we summarize current knowledge of how protein arginine methylation contributes to pre-mRNA splicing and discuss how this modification may help tune the structural and functional plasticity of the spliceosome.
RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels and are essential mediators of post-transcriptional gene regulation in a wide range of physiological and pathological processes. The Rbm24/38 family is a conserved group of RRM-containing RBPs. In invertebrates, Rbm24/38 homologs are generally present as single-copy genes, whereas vertebrates possess two paralogs, Rbm24 and Rbm38, reflecting the progressive elaboration of posttranscriptional regulatory networks during evolution. Functional evidence for non-vertebrate Rbm24/38 homologs remains limited; the nematode protein SUP-12 has been primarily implicated in the regulation of pre-mRNA splicing during myogenesis. By contrast, vertebrate Rbm24 and Rbm38 exhibit broader spatial expression patterns across multiple tissues. Although their expression domains partially overlap, they also display clear gene- and species-specific differences. Functionally, vertebrate Rbm24 and Rbm38 contribute to multilayered post-transcriptional regulation through mechanisms such as alternative splicing, mRNA stability control, and alternative polyadenylation. In addition, regulatory features including isoform diversity, phase-separation potential, and post-translational modifications may further expand their functional versatility, enabling them to coordinate cell fate decisions and tissue homeostasis in distinct physiological contexts. In this review, we summarize recent advances in the evolution, structure, expression, molecular regulation, and biological functions of the Rbm24/38 family. We highlight its conserved features and functional diversification, as well as key unresolved questions regarding its evolution and specialization across metazoans.
MicroRNA-mediated gene regulation occurs within spatially organized intracellular environments and is governed by dynamic molecular interactions that unfold across defined kinetic timescales. Although classical models emphasize sequence complementarity between microRNAs (miRNAs) and their target transcripts, growing evidence indicates that the outcomes of miRNA-target interactions vary widely across cellular contexts and cannot be explained solely by seed pairing or steady-state expression levels. These observations suggest that additional regulatory layers shape the efficiency and fate of miRNA-mediated silencing. In this Review, we examine how the spatial organization of the cell structures miRNA activity across distinct intracellular microenvironments, where the local availability of Argonaute (AGO)-containing RNA-induced silencing complexes (RISCs), target RNAs and regulatory cofactors influences the probability that RISCs encounter and productively engage their targets. We further explore the temporal dimension of miRNA regulation, including Argonaute loading and turnover, the dwell time of RISC-target interactions, miRNA stability and target transcript lifetimes. Recent advances in quantitative and high-resolution approaches for studying RNA dynamics in living cells are beginning to reveal these regulatory processes directly. Together, these observations support a spatiotemporal kinetic model of miRNA regulation, in which intracellular organization and molecular dynamics jointly determine the probability and efficiency of gene silencing. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms.
