Regulatory RNA (ncRNA)

Regulatory RNAs represent a diverse and extensive class of non-coding RNA (ncRNA) molecules that serve as master regulators of gene expression across all biological domains [1, 11]. Unlike protein-coding messenger RNAs, regulatory RNAs such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs) modulate cellular processes by interacting with DNA, other RNAs, or proteins to control transcription, splicing, and translation [5, 11, 18]. Dysregulation of these molecules is strongly linked to the pathogenesis of various human diseases, including cancer, where they may act as oncogenes or tumor suppressors, and rare genetic conditions caused by improper gene silencing or splicing [2, 6, 8]. Consequently, regulatory RNAs have become prominent therapeutic targets and tools for new classes of drugs, such as antisense oligonucleotides (ASOs) and RNA interference (RNAi) therapies, which can precisely modulate previously 'undruggable' genetic targets [3, 7, 10]. Modern drug discovery efforts focus on optimizing the delivery and stability of these molecules while minimizing off-target effects and immune-mediated side effects [4, 7].

Other names

Non-coding RNAncRNAFunctional RNASmall regulatory RNA (sRNA)Riboregulator

Drugs targeting or utilizing regulatory RNA act via several mechanisms including RNA interference (RNAi) through the RISC complex, RNase H-dependent degradation of target transcripts by antisense oligonucleotides, steric blocking of splicing sites to induce exon skipping, and direct structural binding by small molecules to modulate RNA-protein interactions or splicing [3, 4, 8, 11].