RNA-Modifying Molecules: From RNA Structure and Interactomes to Therapeutic use

The field of RNA biology has rapidly evolved from viewing RNA as a intermediary in gene expression to recognizing it as a multifaceted, druggable molecular machine with highly structured and dynamic properties. Recent advances have illuminated the complexity of RNA folding landscapes, the formation of distinct structural features such as riboswitches and aptamers, and the ability of RNA to engage in intricate networks of interactions with proteins, small molecules, and other RNAs. Disease-associated RNAs, in particular, have been shown to create unique pockets suitable for therapeutic targeting; a paradigm shift reflected in the growing pipeline of small molecules and oligonucleotides directed against diverse RNA species. However, despite encouraging breakthroughs, understanding of the molecular mechanisms underlying RNA recognition and modulation remains incomplete, with challenges in specificity, selectivity, off-target effects, and the translation of structural insights into safe and effective therapeutics. While pioneering drugs like risdiplam and advances in antisense technologies have proved the concept of RNA-targeted therapies, many aspects of RNA structure, interactomes, and long-term consequences of intervention require deeper investigation.This Research Topic aims to integrate multidisciplinary perspectives on the foundational and translational aspects of RNA-modifying molecules. We seek to address key questions including: How do small molecules and oligonucleotides recognize and modulate RNA structures or RNA–protein complexes? What are the principles guiding selective targeting versus promiscuous binding? How can artificial intelligence and structure-based methods expedite RNA drug discovery? What are the most promising strategies and challenges for treating specific diseases by modulating RNA processing, splicing, or editing? And crucially, what are the long-term safety ramifications and off-target effects associated with RNA-directed interventions? By gathering mechanistic, chemical, structural, computational, and clinical advances, the topic aims to foster a more comprehensive understanding of RNA as a versatile target for therapeutic innovation.This Research Topic encompasses both foundational and translational research in the discovery, development, and application of RNA-modifying molecules, with a focus on drug-like interactions, mechanisms of action, and clinical relevance. Both basic research and disease-oriented studies are in scope, but work focused purely on canonical mRNA or protein-centric approaches will not be prioritized. To gather further insights in these areas, we welcome articles addressing, but not limited to, the following themes:o The structural dynamics and druggability of RNA moleculeso Design and characterization of small molecules that bind and modulate RNA structureo Mechanisms and therapeutics targeting RNA–protein interactions and aggregateso Modulation of RNA splicing, processing, and editing pathwayso Development and application of antisense oligonucleotides, siRNAs, miRNA therapeutics, and CRISPR–RNA toolso Artificial intelligence and in silico approaches to RNA structure prediction, motif discovery, and drug screeningo Translational studies of RNA-targeted therapies for diverse diseaseso Evaluation of safety, selectivity, transcriptome-wide effects, and off-target biology of RNA-modulating agents Topic editors: Shusheng Wang, Andrea Cerase Source: https://www.frontiersin.org/research-topics/79621/rna-modifying-molecules-from-rna-structure-and-interactomes-to-therapeutic-use