Editorial: RNA regulation mechanisms in microbial-host interactions

The Research Topic "RNA Regula�on Mechanisms in Microbial-Host Interac�ons" was curated to systema�cally explore this complex regulatory landscape, highligh�ng novel molecular mechanisms, technological advancements, and poten�al therapeu�c applica�ons. This collec�on brings together six high-quality ar�cles that collec�vely advance our understanding of how RNA regula�on shapes the outcomes of microbial infec�ons, spanning bacterial and viral pathogenesis, the development of innova�ve detec�on tools, and the emergence of RNA-based therapeu�cs.A major fron�er in contemporary RNA biology is epitranscriptomics-the study of biochemical modifica�ons on RNA molecules and their func�onal consequences. In their original research ar�cle, Zou et al. employed cu�ng-edge direct RNA sequencing technology to inves�gate the macrophage response to Mycobacterium tuberculosis (Mtb) infec�on(htps://doi.org/10.3389/fcimb.2025.1689553). Their comprehensive study reveals mul�layered epitranscriptomic remodeling in host cells, iden�fying specific RNA modifica�ons that correlate with dis�nct infec�on stages and immune ac�va�on states. These findings offer new molecular targets for understanding tuberculosis pathogenesis and may inform the development of host-directed therapies.Complemen�ng this focus on modified coding RNAs, Miao et al. shi�ed aten�on to the emerging class of non-coding RNAs, specifically circular RNAs (circRNAs), during viral infec�on(htps://doi.org/10.3389/fcimb.2025.1654185 ). Inves�ga�ng Vesicular Stoma��s Virus (VSV) as a model system, they provided comprehensive profiling of both host-derived and virus-encoded circRNAs. Their findings highlight the dynamic differen�al expression of these excep�onally stable RNA molecules and suggest they may func�on as molecular sponges for miRNAs or sequester RNA-binding proteins, thereby fine-tuning the host an�viral response. This study reinforces the emerging concept that circRNAs are func�onal players in the host-virus interactome rather than mere splicing byproducts or transcrip�onal noise.The interplay between viral sequences and host physiology extends far beyond acute infec�on episodes. Li et al. present intriguing findings on the unexpected impact of endogenous viral elements (EVEs) on human health, specifically in the context of glioma pathogenesis(htps://doi.org/10.3389/fcimb.2024.1474492). They demonstrate that EVEs-remnants of ancient viral infec�ons integrated into the human genome-can profoundly influence glioma clinical phenotypes by inducing the expression of the stem cell transcrip�on factor OCT4 in host cells. This study elegantly bridges the tradi�onally separate fields of virology and oncology, sugges�ng that these "fossilized" viral remnants in our genome are not dormant relics but can be reac�vated under specific cellular contexts to drive pathological processes. This work provides a novel perspec�ve on the longterm evolu�onary and pathological consequences of microbial-host co-evolu�on, raising important ques�ons about the broader roles of EVEs in human disease.Advancing this rapidly evolving field requires robust and innova�ve methodologies. Two ar�cles in this Research Topic directly address the technological needs of the research community. Ghosh et al. provide a comprehensive and �mely review of emerging RNA-centric technologies specifically designed to probe RNA-protein interac�ons in viral systems(htps://doi.org/10.3389/fcimb.2025.1580337 ). Focusing on posi�ve-sense single-stranded RNA (+ssRNA) viruses-which represent major human pathogens-they systema�cally discuss how these cu�ng-edge tools are essen�al for decoding viral life cycles and iden�fying novel an�viral targets. Their review highlights techniques ranging from classic crosslinking and immunoprecipita�on methods to state-of-the-art single-molecule imaging approaches.On the diagnos�c and surveillance front, Que et al. introduce the "HPD-Kit," a comprehensive and userfriendly toolkit for pathogen detec�on and molecular analysis(htps://doi.org/10.3389/fcimb.2025.1580165 ). In an era where rapid, accurate, and cost-effec�ve iden�fica�on of pathogens is cri�cal for public health preparedness and outbreak response, this toolkit represents a prac�cal transla�on of molecular biology principles into ac�onable diagnos�c solu�ons. The HPD-Kit aims to streamline the pathogen detec�on process and improve real-�me surveillance of infec�ous agents, with par�cular relevance for resource-limited se�ngs.Ul�mately, understanding the fundamental mechanisms of RNA regula�on in infec�on aims to foster the development of novel therapeu�c interven�ons. He et al. contribute a systema�c review and comprehensive bibliometric analysis examining the global landscape of small interfering RNA (siRNA) therapeu�c development(htps://doi.org/10.3389/fcimb.2025.1697880 ). By mapping research trends, iden�fying knowledge hotspots, and analyzing collabora�ve networks in this field, they illustrate how founda�onal research into RNA interference mechanisms is being progressively translated into clinical strategies to combat microbial infec�ons. Their analysis confirms that RNA-based therapeu�cs represent a rapidly maturing field with immense poten�al to address the growing threat of an�microbial resistance, offering precision medicine approaches that could complement or even replace tradi�onal an�microbial agents.The ar�cles presented in this Research Topic collec�vely illustrate the remarkable breadth and depth of RNA regula�on in microbial-host interac�ons. From the epitranscriptomic remodeling of immune cells and the circRNA landscapes of viral infec�ons to the pathological roles of endogenous viral elements, these studies reveal that RNA serves as a central architect of the host-pathogen interface.Looking forward, several exci�ng avenues warrant further inves�ga�on. Future research should increasingly integrate mul�-omics approaches, combining epitranscriptomics with proteomics and single-cell genomics to achieve holis�c understanding of host-pathogen dynamics. Advanced spa�al transcriptomics and real-�me imaging technologies promise to reveal how RNA regula�on varies across �ssue microenvironments and infec�on stages. The success of mRNA vaccines against COVID-19 has demonstrated the tremendous poten�al of RNA-based therapeu�cs, encouraging explora�on of circRNAs, self-amplifying RNAs, and host-directed therapies that manipulate RNA regulatory networks to enhance immunity while minimizing resistance development. Addi�onally, ar�ficial intelligence and machine learning approaches will become increasingly important for predic�ng RNA structures and interac�ons from high-throughput data, accelera�ng the discovery of novel therapeu�c targets. Finally, evolu�onary perspec�ves examining how RNA regulatory mechanisms have co-evolved in pathogens and hosts will provide insights into vulnerability points for therapeu�c exploita�on.We hope this collec�on serves as both a comprehensive resource and a catalyst for future inves�ga�ons, encouraging researchers worldwide to delve deeper into the "RNA world" to uncover the hidden regulatory mechanisms that govern the delicate balance between health and disease.